Research ArticleClinical Studies

Investigative Clinical Study on Prostate Cancer Part VIII: Prolactin Hormone and the Pituitary-Testicular-Prostate Axis at the Time of Initial Diagnosis and Subsequent Cluster Selection of the Patient Population after Radical Prostatectomy

ANTONIO B. PORCARO, CLAUDIO GHIMENTON, ALDO PETROZZIELLO, FILIPPO MIGLIORINI, MARIO ROMANO, TEODORO SAVA, BEATRICE CARUSO, CLAUDIO COCCO, STEFANO ZECCHININI ANTONIOLLI, VINCENZO LACOLA, EMANUELE RUBILOTTA, CARMELO MONACO and LUIGI COMUNALE
Anticancer Research April 2012, 32 (4) 1499-1506;

Abstract

Aim: To evaluate the prolactin hormone (PRL) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer and the subsequent cluster selection of the patient population after radical prostatectomy in relation to clinical and pathological variables. Patients and Methods: Ninety-two operated prostate cancer patients were retrospectively reviewed. No patient had previously received hormonal treatment. The investigated variables included PRL, follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), total prostate specific antigen (PSA), percentage of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi) and age. Empirical PRL correlations and multiple linear predictions were investigated along the pituitary testis prostate axis in the different groups of the prostate cancer population and clustered according to pT (2a/b, 3a, 3b/4) status. The patient population was classified according to the log(10) PRL/V+ ratio and clustered as follows: group A (log(10) PRL/V+ ≤1.5), B (1.5< log(10)PRL/V+ ≤2.0) and C (log(10) PRL/V+ >2.0). Simple linear regression analysis of V+ predicting PRL was computed for assessing the clustered model and analysis of variance was performed for assessing significant differences between the groups. Results: PRL was independently predicted by FSH (p=0.01), LH (p=0.008) and P+ (p=0.06) in low-stage prostate cancer (pT2a/b). Interestingly, PRL was independently predicted by LH (p=0.03) and FSH, TT, FT, PSA, bGS, pGS, V+, Wi and age (all at p=0.01) in advanced stage-disease (pT3b/4). V+ was also significantly correlated (r=0.47) and predicted by P+ (p<0.0001) in the prostate cancer population. PRL was significantly correlated and predicted by V+ when the patient population was clustered according to the log(10)PRL/V+ ratio in group A (p=0.008), B (p<0.0001) and C (p<0.0001). Moreover, the three groups had significantly different mean values of PRL (p<0.0001), PSA (p=0.007), P+ (p=0.0001), V+ (p<0.0001), Wi (p=0.03), bGS (p=0.008), pGS (p=0.003); also, groups A, B and C had significant different pGS (p=0.03), pT (p=0.0008) and pR (p=0.01) frequency distributions. Conclusion: At diagnosis, in an operated prostate cancer population, PRL was significantly correlated and independently predicted along the pituitary testis prostate axis in high-stage disease; V+ was also significantly correlated and predicted by P+. Because of the high correlation and prediction of PRL by both V+ and P+, the prostate cancer population at diagnosis was clustered according to the log(10)PRL/V+ ratio into groups A, B and C that, in theory, might be models with prognostic potential and clinical applications in the prostate cancer population. However, confirmatory studies are needed.

The endocrine system related to prostate cancer biology includes the hypothalamus, the pituitary gland, the testes and the adrenals. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are secreted from the gonadotroph cells located in the anterior pituitary. Prolactin (PRL) is a polypeptide hormone which is secreted by the pituitary lactotroph cells. The interstitial cells of Leydig are responsible for the production of 95% of all circulating androgen in the form of testosterone. Approximately 98% of circulating androgens are bound to plasma proteins, including a specific beta-globulin, testosterone-binding globulin (TeBG). The free testosterone in the blood is the physiologically important fraction. LH, FSH, PRL, androgens and estrogens regulate prostate physiology.

Etiological and stimulatory factors relating to prostate cancer are still unclear. Literature evidence shows that prostate cancer is androgen dependent (1), increases the levels of prostate-specific antigen (PSA) (2), is related to PSA growth rate for extension and prognosis (3, 4), and in pretreatment total testosterone (TT) and free testosterone (FT) serum levels may both be abnormal (5-12). Human benign prostatic hyperplasia and prostate cancer tissues have been found to express LH and FSH receptors (13-17). These findings suggest that gonadotrophins may promote cancer either indirectly by stimulating testicular production of hormones or directly through their receptors located in the prostate gland (18). Locally produced PRL has been documented in prostate tumors and has tumor growth potency, acting via autocrine/paracrine mechanisms; a novel class of compounds with therapeutic potential to target PRL receptors (PRLR) signaling, namely competitive PRLR antagonists, have also been developed (19, 20).

Prostate cancer is an interesting tumor for clinical endocrine investigation but much of prostate cancer physiopathology is unknown (21). The pituitary axis in prostate cancer has been investigated and evidence suggests that the tumor may produce a substance that alters the normal function of the pituitary–testicular axis which results in abnormal LH and FSH serum levels (5, 9-12, 22-29). It has been suggested that the impact of prostate cancer on the hypothalamic–pituitary axis may be more profound in high-grade prostate cancer (27), but this hypothesis has not been confirmed (30).

This study aimed at evaluating PRL physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer, with subsequent cluster selection of the patient population after radical prostatectomy in relation to clinical and pathological variables.

Patients and Methods

The study retrospectively reviewed 92 prostate cancer patients who underwent standard radical retropubic prostatectomy (RRP). The total patient population under the testosterone study, still open and progressing, is over 235 individuals, but this article does not include patients who were not simultaneously assessed for pituitary hormones. The descriptive statistics of the patient population are shown in Table I. All patients had histologically proven carcinoma of the prostate and had not previously received 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement treatment. The 14-core transrectal ultrasound scan (TRUS)-guided prostate biopsy technique was routinely used and additional cores were obtained when a lesion on either TRUS or digital rectal examination was evident. After informed signed consent, simultaneous pretreatment serum samples were obtained from a cubital vein, at least one month after TRUS biopsy between 8.00–8.30 a.m. for measuring serum PRL, FSH, LH, TT, FT and PSA levels. The samples were analyzed at the same laboratory of our hospital. PRL (range: 3.07-20.05 μg/l), FSH (range: 1.0-14 IU/l), LH (range: 2.0-10 IU/l), TT (normal range: 9-29 nmol/l) and PSA (normal range: 2-4 μg/l) were measured by immunochemiluminescent test performed by ADVIA Centaur XP Immunoassay System (Siemens Company). FT (normal range: 31-163 pmol/l) was measured by immunoradiometric test (DSL, USA). The prostatectomy specimens were fixed in toto overnight (10% neutral buffered formhaldeyde), coated with India ink and then weighed. Tissue sections of 4 μm were prepared in standard fashion and stained with hematoxylin and eosin. Patients were classified according to primary tumor stage, lymph node and metastatic status, using the TNM categories recommended by the 1997 International Union Against Cancer TNM classification system (31). Seminal vesicle invasion was defined as tumor involvement of the muscular wall (pT3b). Invasion of the bladder neck was staged as pT4 disease. Surgical margins (pR) were stated as free (pR-) or invoved by cancer (pR+). Tumors were graded according to the Gleason grading system and the Gleason score was computed after summing the two patterns structuring the tumor. Overall cancer volume was estimated as a percentage of the prostate volume (V+). Biopsy and prostatectomy specimens were assessed by an experienced pathologist.

View this table:
Table I.

Summary and descriptive statistics of the patient population (n=92).

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Table II.

Correlations of prolactin (PRL) with other hormones/factors and predictions along the pituitary-testis-prostate axis of the prostate cancer population (n=92) clustered into pT and pR groups.

Statistical methods. Continuous variables investigated were as follows: PRL, FSH, LH, TT, FT, PSA, percentage of positive cores at TRUS biopsy (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), V+ and overall prostate weight (Wi) in grams. Empirical PRL correlations and multiple linear predictions were investigated along the pituitary testis prostate axis in the different groups of the prostate cancer population clustered according to pT (2a/b, 3a, 3b/4) status. Analysis of variance was performed in order to detect statistical significance of the variables between the pT groups.

The patient population was classified according to the log(10) PRL/V+ ratio and clustered as follows: group A (log(10) PRL/V+ ≤1.5), B (1.5< log(10)PRL/V+ ≤2.0) and C (log(10) PRL/V+ >2.0). Simple linear regression analysis of V+ predicting PRL was computed for assessing the clustered model; one observation was excluded from the analysis due to being considered an outlier (PRL=47.69). Analysis of variance was computed for assessing significant differences of PRL, FSH, LH, TT, FT, PSA, P+, bGS, pGS, V+, Wi and age between groups A, B and C. The pG, pT and pR groups were related to the A, B and C clusters by contingency tables and the Chi-squared test was performed in order to detect statistical significance. Scatter pots of V+ predicting PRL were computed for each pT group, which was also subclustered into group A, B and C, according to the log(10) PRL/V+ ratio.

Results

PRL correlations and predictions along the pituitary testis prostate axis are reported in Table II. PRL was independently predicted by FSH (p=0.01), LH (p=0.008) and P+ (p=0.06) in low-stage prostate cancer (pT2a/b) (V+ approaching significance, p=0.09). Interestingly, PRL was independently predicted by FSH (p=0.01), LH (p=0.03), TT (p=0.01), FT (p=0.01), PSA (p=0.01), bGS (p=0.01), pGS (p=0.01), V+ (p=0.01), Wi (p=0.01) and age (p=0.01) in advanced prostate cancer (pT3b/4). The pT groups significantly differed in mean values for PSA (p=0.01), P+ (p=0.002), V+ (p<0.0001), bGS (p=0.02) and pGS (p=0.0001) (Table III). V+ was significantly correlated (r=0.47) and predicted by P+ (p<0.0001) in the prostate cancer population (Figure 1). As shown in Table IV and Figure 2, PRL was significantly correlated and predicted by V+ when the patient population was clustered according to the log(10) PRL/V+ ratio into group A (p=0.008), B (p<0.0001) and C (p<0.0001). Moreover, as reported in Table IV-A, the three groups had significantly different mean values of PRL (p<0.0001), PSA (p=0.007), P+ (p=0.0001), V+ (p<0.0001), Wi (p=0.03), bGS (p=0.008) and pGS (p=0.003); groups A, B and C also had significantly different pGS (p=0.03), pT (p=0.0008) and pR (p=0.01) frequency distributions (see Table V). The different A, B and C sub clusters in the pT2a/b, pT3a and pT3b/4 groups are depicted in Figure 3.

Figure 1.
Figure 1.

P+ predicting V+ plot for the prostate cancer population (n=92). P+ and V+ are significantly (p<0.0001) correlated (r=0.47).

Figure 2.
Figure 2.

V+ predicting PRL in the prostate cancer population (n=91) clustered into groups A, B and C according to to the log(10)PRL/V+ ratio.

Discussion

PRL correlation to prostate cancer is unclear, controversial and not fully investigated. It has been shown that PRL did not correlate with any prostate cancer variable (6, 9); however, it has also been demonstrated that on univariate analysis, PRL was inversely associated with PSA, but that correlation disappeared on the multivariate analysis (32). The prognostic value of PRL in the prostate cancer population is also unclear; it has been shown that serum PRL levels were significantly lower in patients with metastatic prostate cancer with a good response to hormonal treatment (12), but they did not relate to survival (11). The present study, investigating empirical PRL correlations in the prostate cancer population, showed that PRL was independently correlated and predicted along the pituitary testis prostate axis in locally advanced prostate cancer (see Table II), suggesting a close relationship to aggressive cancer biology and prognostic potential in prostate cancer progression (33-36). The present results confirmed our previous investigations (37, 38) and showed that testis hormones (FT and TT) might have a key role in prostate cancer biology along the pituitary-testis prostate axis, expressing complicated feedback systems, which, in part, might be explained by both linear and non-linear mathematical laws (39-42). We also showed that V+ was highy correlated and predicted by P+ (Figure 1), suggesting that P+ might be an effective preoperative clinical tool for predicting both PRL and tumor volume. The present findings also confirmed our previous results where we showed that PRL was independently predicted by P+ at diagnosis in the prostate cancer population (43).

Figure 3.
Figure 3.

Prolactin (PRL) versus V+ plots in pT2a/b (A), pT3a (B) and pT3b/4 (C) of the prostate cancer population (n=92). Each pT group is subclustered by the log(10)PRL/V+ ratio into groups A, B and C.

View this table:
Table III.

Analysis of variance of the patient population (n=92) clustered according to the pT status.

View this table:
Table IV.

Analysis of variance and simple linear regression analysis of the prostate cancer population (n=91) clustered according to the PRL/V+ ratio.

View this table:
Table V.

Contigency table relating pGS, pT and pR groups to the PRL/V+ clusters in the patient population (n=92).

The significant correlation and prediction of PRL with V+ allowed us to cluster the patient population into groups (A, B, C), according to the log(10) PRL/V+ ratio (see Figure 2). Serum PRL levels were all significantly predicted by V+ in the three clusters (see Table IV-B) and significantly differred for PRL, PSA, P+, V+, Wi, bGS, pGS, pT and pR (see Tables IV and V), suggesting that this model might have a potential prognostic role in prostate cancer progression (33-36). Moreover, the evidence of our results showed the log(10) PRL/V+ ratio selected significant potential prognostic clusters in which the risk of progression might be assessed as high for group A, intermediate for group B and low for group C.

It has been assessed that core biopsy of the prostate may under- and overgrade the final combined Gleason grade (44); indeed, an exact Gleason score match is present in 41% of the cases, while 48% are under- and 17% overgraded (45); the number of positive cores is also a significant predictor of upgrading (46). The present study shows that the risk of over- and undergrading prostate cancer might be reduced by clustering the patient population according to the log(10) PRL/V+ ratio after predictng V+ by P+ (see Figures 1-2 and Tables IV-V); moreover, our findings have been confirmed by literature reports showing that PRL protein was correlated to high Gleason scores (47) and was expressed in a large proportion of hormone-refractory clinical human prostate carcinomas and in prostate cancer metastases (48). These results also concord with literature findings showing that high serum PRL levels reduced the risk of prostate cancer in the male popolation (49) and increased the weight of the prostate in experimental animal models (50).

Interestingly, the pT3b/4 group exhibited lower mean values of PRL and Wi, as well as higher mean levels of TT and FT, and age, but these differences did not reach statistical significance (Table III). PRL did not show any empirical significant correlation to the variables in the pT3a prostate cancer group (Table II). In theory, these results might both be explained by Figure 3 which shows that each pT group might be subclustered into A (high risk), B (intermediate risk) and C (low risk) potential prognostic subsets.

The present investigation was limited by the small number of patients, but revealed new findings in prostate cancer physiopathology along the pituitary testis prostate axis; it also suggests a model which might be challenging for its potential applications in clinical prostate cancer. However, confirmatory studies are needed.

Conclusion

At diagnosis, in a prostate cancer population undergoing RRP, PRL was significanlty correlated and independently predicted along the pituitary testis prostate axis in advanced-stage disease; V+ was also significantly correlated and predicted by P+. Due the high correlation and prediction of PRL by both V+ and P+, the prostate cancer population at diagnosis was clustered according to the log(10) PRL/V+ ratio into groups of low, intermediate and high risk which in theory might express prognostic potential and have clinical application in the prostate cancer population. However, confirmatory studies are needed.

  • Received February 6, 2012.
  • Revision received March 11, 2012.
  • Accepted March 12, 2012.

References

  1. ↵
    1. Huggins C,
    2. Hodges CV
    : Studies on prostate cancer. I: The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1: 293-297, 1941.
    OpenUrlFREE Full Text
  2. ↵
    1. Stamey TA,
    2. Yang N,
    3. Hay AR,
    4. McNeal JE,
    5. Freiha FS,
    6. Redwine E
    : Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 317: 909-916, 1987.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Stenman UH,
    2. Abrahamsson PA,
    3. Aus G,
    4. Lilja H,
    5. Bangma C,
    6. Hamdy FC,
    7. Boccon-Gibod L,
    8. Ekman P
    : Prognostic value of serum markers for prostate cancer. Scand J Urol Nephrol Suppl 216: 64-81, 2005.
    OpenUrlPubMed
  4. ↵
    1. Monda JM,
    2. Myers RP,
    3. Bostwick DG,
    4. Oesterling JE
    : The correlation between serum prostate-specific antigen and prostate cancer is not influenced by the serum testosterone concentration. Urology 46: 62-64, 1995.
    OpenUrlPubMed
  5. ↵
    1. Imamoto T,
    2. Suzuki H,
    3. Fukasawa S,
    4. Shimbo M,
    5. Inahara M,
    6. Komiya A,
    7. Ueda T,
    8. Shiraishi T,
    9. Ichikawa T
    : Pretreatment serum testosterone level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy. Eur Urol 47: 308-312, 2005.
    OpenUrlCrossRefPubMed
  6. ↵
    1. Mearini L,
    2. Costantini E,
    3. Zucchi A,
    4. Mearini E,
    5. Bini V,
    6. Cottini E,
    7. Porena M
    : Testosterone levels in benign prostatic hypertrophy and prostate cancer. Urol Int 80: 134-140, 2008.
    OpenUrlPubMed
    1. Yano M,
    2. Imamoto T,
    3. Suzuki H,
    4. Fukasawa S,
    5. Kojima S,
    6. Komiya A,
    7. Naya Y,
    8. Ichikawa T
    : The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening. Eur Urol 51: 375-380, 2007.
    OpenUrlCrossRefPubMed
    1. Ide H,
    2. Yasuda M,
    3. Nishio K,
    4. Saito K,
    5. Isotani S,
    6. Kamiyama Y,
    7. Muto S,
    8. Horie S
    : Development of a nomogram for predicting high-grade prostate cancer on biopsy: the significance of serum testosterone levels. Anticancer Res 28: 2487-2492, 2008.
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Miller LR,
    2. Partin AW,
    3. Chan DW,
    4. Bruzek DJ,
    5. Dobs AS,
    6. Epstein JI,
    7. Walsh PC
    : Influence of radical prostatectomy on serum hormone levels. J Urol 160: 449-453, 1998.
    OpenUrlCrossRefPubMed
    1. Olsson M,
    2. Ekstrom L,
    3. Schulze J,
    4. Kjellman A,
    5. Akre O,
    6. Rane A,
    7. Gustafsson O
    : Radical prostatectomy: influence on serum and urinary androgen levels. Prostate 70(2): 200-205, 2010.
    OpenUrlPubMed
  11. ↵
    1. Harper ME,
    2. Pierrepoint CG,
    3. Griffiths K
    : Carcinoma of the prostate: relationship of pretreatment hormone levels to survival. Eur J Cancer Clin Oncol 20(4): 477-482, 1984.
    OpenUrlCrossRefPubMed
  12. ↵
    1. Chen SS,
    2. Chen KK,
    3. Lin AT,
    4. Chang YH,
    5. Wu HH,
    6. Chang LS
    : The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis. BJU Int 89(7): 710-713, 2002.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Tao YX,
    2. Bao S,
    3. Ackermann DM,
    4. Lei ZM,
    5. Rao CV
    : Expression of luteinizing hormone/human chorionic gonadotropin receptor gene in benign prostatic hyperplasia and in prostate carcinoma in humans. Biol Reprod 56: 67-72, 1997.
    OpenUrlCrossRefPubMed
    1. Dirnhofer S,
    2. Berger C,
    3. Hermann M,
    4. Steiner G,
    5. Madersbacher S,
    6. Berger P
    : Coexpression of gonadotropic hormones and their corresponding FSH-LH and LH/CG-receptors in the human prostate. Prostate 35: 212-220, 1998.
    OpenUrlCrossRefPubMed
    1. Ben-Josef E,
    2. Yang SY,
    3. JI TH,
    4. Bidart JM,
    5. Garde SV,
    6. Chopra DP,
    7. Porter AT,
    8. Tang DG
    : Hormone-Refractory prostate cancer cell express functional follicle-stimulating hormone receptor (FSHR). J Urol 161: 970-976, 1999.
    OpenUrlCrossRefPubMed
    1. Mariani S,
    2. Salvatori L,
    3. Basciani S,
    4. Arizzi M,
    5. Franco G,
    6. Petrangeli E,
    7. Spera G,
    8. Gnessi L
    : Expression and cellular localization of follicle-stimulating hormone receptor in normal human prostate, benign prostatic hyperplasia and prostate cancer. J Urol 175: 2072-2077, 2006.
    OpenUrlCrossRefPubMed
  17. ↵
    1. Radu A,
    2. Pichon C,
    3. Camparo P,
    4. Antoine M,
    5. Allory Y,
    6. Couvelard A,
    7. Fromont G,
    8. Thu Vu Hai M,
    9. Ghinea N
    : Expression of follicle-stimulating hormone receptor in tumor blood vessels. N Engl J Med 363: 1621-30, 2010.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Huhtaniemi
    : Are gonadotropins tumorogenic – A critical review of clinical and experimental data. Molecular and Cellular Endocrinology 329: 56-61, 2010.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Bernichtein S,
    2. Touraine P,
    3. Goffin V
    : New concepts in Prolactin biology. Journal of Endocrinology 206: 1-11, 2010.
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Jacobson EM,
    2. Hugo ER,
    3. Tuttle TR,
    4. Papoian R,
    5. Ben-Jonathan N
    : Unexploited therapies in breast and prostate cancer: blockade of the prolactin receptor. Trends Endocrinol 21(11): 691-698, 2010.
    OpenUrlCrossRefPubMed
  21. ↵
    1. Walsh PC
    : Chemoprevention in prostate cancer. N Engl J Med 362(13): 1237-1238, 2010.
    OpenUrlCrossRefPubMed
  22. ↵
    1. Hammond GL,
    2. Kontturi M,
    3. Maattala P,
    4. Puukka M,
    5. Vihko R
    : Serum FSH, LH and prolactin in normal males and patients with prostatic diseases. Clin Endocrinol 7(2): 129-135, 1977.
    OpenUrlCrossRefPubMed
    1. Kumar VL,
    2. Wafhwa SN,
    3. Kumar V,
    4. Farooq A
    : Androgen, estrogen, and progesterone receptor contents and serum hormone profiles in patients with benign hypertrophy and carcinoma of the prostate. J Surg Oncol 44(2): 122-128, 1990.
    OpenUrlPubMed
    1. Anderson SO,
    2. Adami HO,
    3. Bergstrom R,
    4. Wide B
    : Serum pituitary and sex steroid hormone levels in the etiology of prostatic cancer – a population-based case-control study. Br J Cancer 68: 97-102, 1993.
    OpenUrlPubMed
    1. Schatzl G,
    2. Madersbacher S,
    3. Thurridl T,
    4. Waldmuller J,
    5. Kramer G,
    6. Haitel A,
    7. Marberger M
    : High-grade prostate cancer is associated with low serum testosterone levels. Prostate 47(1): 52-58, 2001.
    OpenUrlCrossRefPubMed
    1. Hilz H,
    2. Graefen M,
    3. Noldus J,
    4. Hammerer P,
    5. Knabbe C,
    6. Huland E,
    7. Huland H
    : Advanced prostate cancer is associated with a decrease in serum luteinizing hormone. Eur Urol 38(3): 243-249, 2000.
    OpenUrlPubMed
  27. ↵
    1. Madersbacher S,
    2. Shatzl G,
    3. Bieglmayer C,
    4. Reiter BW,
    5. Gassner C,
    6. Berger P,
    7. Zidek T,
    8. Marberger M
    : Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal axis. Urology 60: 869-874, 2002.
    OpenUrlPubMed
    1. Sofikerim M,
    2. Eskicorapaci S,
    3. Oruc O,
    4. Ozen H
    : Hormonal predictors of prostate cancer. Urol Int 79: 913-918, 2007.
    OpenUrl
  29. ↵
    1. Imamoto T,
    2. Suzuki H,
    3. Yano M,
    4. Kawamura K,
    5. Kamiya N,
    6. Araki K,
    7. Komiya A,
    8. Naya Y,
    9. Shiraishi T,
    10. Ichikawa T
    : Does the presence of prostate cancer affect serum testosterone levels in clinically localized prostate cancer patients? Prostate Cancer Prostatic Dis 12(1): 78-82, 2009.
    OpenUrlPubMed
  30. ↵
    1. Fodstad P,
    2. Bjoro T,
    3. Torlakovic G,
    4. Fossa SD
    : No association of serum gonadal or pituitary hormone with prognostic parameters in stages T1 to T3 pN0M0 prostate cancer. J Urol 168: 1188-1192, 2002.
    OpenUrlCrossRefPubMed
  31. ↵
    1. Flemming ID,
    2. Cooper JS,
    3. Henson DE,
    4. Hutte RVP,
    5. Kennedy BJ,
    6. Murphy GP,
    7. O'Sullivan B,
    8. Sobin LH,
    9. Yarbro JN
    (eds.).: American Joint Committee on Cancer Staging Manual, 5th ed. Philadelphia, JP Lippincott, pp. 219-222, 1997.
  32. ↵
    1. Vijayakumar S,
    2. Quadri SF,
    3. Dong L,
    4. Ignacio L,
    5. Kathuria INS,
    6. Sutton H,
    7. Halpern H
    : Results of a study to correlate serum prostate specific antigen and reproductive hormone levels in patients with localized prostate cancer. J Natl Med Assoc 87: 813-819, 1995.
    OpenUrlPubMed
  33. ↵
    1. Pound CR,
    2. Partin AW,
    3. Eisenberger M,
    4. Chan DW,
    5. Pearson JD,
    6. Walsh PC
    : Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281: 1591-1597, 1999.
    OpenUrlCrossRefPubMed
    1. Hull GW,
    2. Rabbani F,
    3. Abbas FA,
    4. Wheeler TM,
    5. Kattan MW,
    6. Scardino PT
    : Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol 167: 528-534, 2002.
    OpenUrlCrossRefPubMed
    1. Freedland SJ,
    2. Humphreys EB,
    3. Mangold LA,
    4. Eisenberger M,
    5. Dorey FJ,
    6. Walsh PC,
    7. Partin AW
    : Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 294: 433-439, 2005.
    OpenUrlCrossRefPubMed
  36. ↵
    1. Cuzik J,
    2. Fisher G,
    3. Kattan MW,
    4. Berney D,
    5. Oliver T,
    6. Foster CS,
    7. Moller H,
    8. Reuter V,
    9. Fearn P,
    10. Eastham J,
    11. Scardino P,
    12. on behalf of the Transatlantic Prostate Cancer Group
    : Long-term outcome among men with conservatively treated localised prostate cancer. Br J of Cancer 95: 1186-1194, 2006.
    OpenUrl
  37. ↵
    1. Porcaro AB,
    2. Petrozziello A,
    3. Migliorini F,
    4. Caruso B,
    5. Cocco C,
    6. Sava T,
    7. Ghimenton C,
    8. Romano M,
    9. Monaco C,
    10. Comunale L
    : Investigative clinical study on prostate cancer Part V: Luteinizing Hormone and the Pituitary-Testicular-Prostate Axis at the Time of Initial diagnosis and subsequent cluster selection of the patient population. Anticancer Res 31: 1071-1078, 2011.
    OpenUrlAbstract/FREE Full Text
  38. ↵
    1. Porcaro AB,
    2. Migliorini F,
    3. Petrozziello A,
    4. Sava T,
    5. Romano M,
    6. Caruso B,
    7. Cocco C,
    8. Ghimenton C,
    9. Zecchini Antoniolli S,
    10. Lacola V,
    11. Rubilottta E,
    12. Monaco C,
    13. Comunale L
    : Investigative clinical study on prostate cancer part VI: Follicle stimulating hormone and the pituitary testicular prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population. Urol Int 88: 150-157, 2012.
    OpenUrlPubMed
  39. ↵
    1. Porcaro AB,
    2. Migliorini F,
    3. Petrozziello A,
    4. Antoniolli SZ,
    5. Rubilotta E,
    6. Lacola V,
    7. Sava T,
    8. Ghimenton C,
    9. Caruso B,
    10. Monaco C,
    11. Comunale L
    : Investigative clinical study on prostate cancer: On the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients. Int Urol Nephrol 42(3): 673-681, 2009.
    OpenUrlPubMed
    1. Porcaro AB,
    2. Monaco C,
    3. Romano M,
    4. Petrozziello A,
    5. Rubilotta E,
    6. Lacola V,
    7. Sava T,
    8. Ghimenton C,
    9. Caruso B,
    10. Antoniolli SZ,
    11. Migliorini F,
    12. Comunale L
    : Investigative clinical study on prostate cancer part II: on the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy. Urol Int 85(2): 152-158, 2010.
    OpenUrlPubMed
    1. Porcaro AB,
    2. Petrozziello A,
    3. Romano M,
    4. Sava T,
    5. Ghimenton C,
    6. Caruso B,
    7. Migliorini F,
    8. Zecchini Antoniolli S,
    9. Rubilotta E,
    10. Lacola V,
    11. Monaco C,
    12. Comunale L
    : Investigative clinical study on prostate cancer Part III: Exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio. Urol Int 85(4): 407-409, 2010.
    OpenUrl
  42. ↵
    1. Porcaro AB,
    2. Petrozziello A,
    3. Migliorini F,
    4. Lacola V,
    5. Romano M,
    6. Sava T,
    7. Ghimenton C,
    8. Caruso B,
    9. Zecchini Antoniolli S,
    10. Rubilottta E,
    11. Monaco C,
    12. Comunale L
    : Investigative clinical study on prostate cancer part IV. On exploring functional relationships of total testosterone and total prostate specific antigen (PSA) in operated prostate cancer patients. Urol Int 86(4): 399-406, 2011.
    OpenUrlPubMed
  43. ↵
    1. Porcaro AB,
    2. Ghimenton C,
    3. Petrozziello A,
    4. Migliorini F,
    5. Romano M,
    6. Sava T,
    7. Caruso B,
    8. Cocco C,
    9. Zecchinini Antoniolli S,
    10. Lacola V,
    11. Rubilotta E,
    12. Monaco C,
    13. Comunale L
    : Investigative clinical study on prostate cancer Part VII: prolactin hormone and the pituitary testicular prostate axis at the time of Initial diagnosis and subsequent cluster selection of the patient population. Anticancer Res 31(11): 3913-3920, 2011.
    OpenUrlAbstract/FREE Full Text
  44. ↵
    1. Lange P,
    2. Narayan P
    : Understaging and undergrading of prostate cancer. Urol Clin North Am 2: 105-124, 1983.
    OpenUrl
  45. ↵
    1. King CR
    : Patterns of prostate cancer biopsy grading: trends and clinical implications. Int J Cancer (Radiat Oncol Invest) 90: 305-311, 2000.
    OpenUrl
  46. ↵
    1. Moussa AS,
    2. Li J,
    3. Soriano M,
    4. Klein EA,
    5. Dong F,
    6. Jones JS
    : Prostate biopsy clinical and pathological variables that predict significant grading changes in patients with intermediate and high grade prostate cancer. BJU Int 103: 43-48, 2008.
    OpenUrlPubMed
  47. ↵
    1. Li H,
    2. Ahonen TJ,
    3. Alanen K,
    4. Xie J,
    5. LeBaron M,
    6. Pretlow TG,
    7. Eally EL,
    8. Zhang Y,
    9. Nurmi M,
    10. Singh B,
    11. Martikainen PM,
    12. Nevalaine MT
    : Activation of signal transducer and activateor of transcription 5 in human prostate cancer is associated with high histological grade. Cancer Res 64: 4774-4782, 2004.
    OpenUrlAbstract/FREE Full Text
  48. ↵
    1. Dagvadori A,
    2. Collins S,
    3. Jomain JB,
    4. Abdulghani J,
    5. Karras J,
    6. Zellweger T,
    7. Li H,
    8. Nurmi M,
    9. Alanen K,
    10. Mirtti T,
    11. Visakorpi T,
    12. Bubendorf L,
    13. Goffin V,
    14. Nevalainen M
    : Autocrine prolactin promotes prostate cancer cell growth via Janus kinase-2-signal transducer and activator of transcription-5a/b signaling pathway. Endocrinology 148: 3089-3101, 2007.
    OpenUrlCrossRefPubMed
  49. ↵
    1. Berinder K,
    2. Akre O,
    3. Granath F,
    4. Hulting AL
    : Cancer risk in hyperprolactinemia patient – a population-based cohort study. Eur J Endocrinol 165(2): 209-215, 2011.
    OpenUrlAbstract/FREE Full Text
  50. ↵
    1. Hernandez ME,
    2. Soto-Cid A,
    3. Rojas F,
    4. Pascual LI,
    5. Aranda-Abreu GE,
    6. Toledo R,
    7. Garcia LI,
    8. Quintanar-Stephano A,
    9. Manzo J
    : Prostate response to prolactin in sexually active male rats. Reprod Biol Endocrinol 4:28: 1-12, 2006.
    OpenUrl
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Investigative Clinical Study on Prostate Cancer Part VIII: Prolactin Hormone and the Pituitary-Testicular-Prostate Axis at the Time of Initial Diagnosis and Subsequent Cluster Selection of the Patient Population after Radical Prostatectomy
ANTONIO B. PORCARO, CLAUDIO GHIMENTON, ALDO PETROZZIELLO, FILIPPO MIGLIORINI, MARIO ROMANO, TEODORO SAVA, BEATRICE CARUSO, CLAUDIO COCCO, STEFANO ZECCHININI ANTONIOLLI, VINCENZO LACOLA, EMANUELE RUBILOTTA, CARMELO MONACO, LUIGI COMUNALE
Anticancer Research Apr 2012, 32 (4) 1499-1506;
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