Abstract
The expression of 11 tumor markers in 129 women with squamous cell compared to 31 women with adenomatous cervical cancer was investigated to detect differences in expression. There was a significantly higher expression of p53, CD4, epidermal growth factor receptor (EGFR), CD44 and stratifin in squamous cell, compared to adenocarcinoma, while there was a higher expression of c-myc in adenocarcinoma. P-53, cyclooxygenase-2 (Cox-2) and c-myc significantly correlated to prognosis in squamous cell carcinoma, but none of the 11 investigated tumor markers had any prognostic value in adenocarcinomas. The prognostic value of individual tumor markers differs with the histological subtype in cervical cancer.
The expression of tumor markers diagnosed by immunohistochemistry is used in a variety of cancer types for prognostic and diagnostic purposes. In cervical cancer, similar tumor markers are often used irrespective of histological type (1). Some studies have included squamous cell, adenosquamous and adenomatous cancer simultaneously in the analyses (2, 3). In this study, the expression of 11 tumor markers and 10-year survival was compared between 129 cases of squamous cell and 31 cases of adenomatous cervical cancer.
Patients and Methods
Women who had been admitted to the Department of Gynecologic Oncology, Norrlands University Hospital, Umeå from 1984 to 1990 were included in the study. The clinical staging according to FIGO (International Federation of Gynecology and Obsterics) and ten-year survival were considered when the expression of tumor markers in pretreatment biopsies in squamous cell and adenomatous cervical cancer was compared. All the women had been treated with radiotherapy and in some cases also surgically in accordance with contemporary routines. The follow-up time was at least ten years. The immunohistochemical staining followed standard methods and the evaluation of expression was assessed by a pathologist blinded to the clinical details. The material has been presented in detail elsewhere (4).
Tumor markers. The expression of c-myc (malignant transformation), Ki-67 (proliferation) and epidermal growth factor receptor (EGFR; proliferation), p53 (tumor suppression), p27 (tumor suppression) and stratifin (cell cycle arrest), E-cadherin (cell-cell adhesion), CD44 (cell-cell adhesion), vascular endothelial growth factor (VEGF; angiogenesis), cyclooxygenase-2 (Cox-2) (prostaglandin synthesis) and CD4 (immune response) were identified.
Results and Discussion
The expression of 6 out of the 11 tumor markers differed significantly between the two histological subtypes of cervical cancer (Table I). Five of them were more highly expressed in squamous cell carcinoma while one (c-myc) showed higher expression in adenocarcinoma. Particularly large differences in expression were observed for CD44, c-myc and stratifin.
The women with adenocarcinoma had a better 10-year survival than those with squamous cell carcinoma (74.2% vs. 58.7%, p=0.10). This was mainly due to the later clinical stage at diagnosis in the squamous cell cancer patients. When the prognostic impact of the tumor markers was analysed, after adjustment for stage dichotomised in IB-IIA and IIB-IV, the expression of p53 was found to be significantly correlated to a favourable outcome, while the expression of c-myc and Cox-2 were significantly correlated to poor ten-year survival in the squamous cell cancer cohort. None of these nor any of the other tumor markers correlated to survival in adenocarcinoma (Table II).
Diffferences in expression of tumor markers between squamous cell and adenomatous cervical carcinoma.
Tumor markers and 10-year survival in adenomatous and squamous cell cervical carcinoma.
The differences in the level of expression of the tumor markers in squamous cell and adenomatous carcinoma cannot be explained by this study. Baltazar et al. found a similar difference in EGFR expression as in the present study but also found a difference in Cox-2 expression (5). The latter might be due to a different method of Cox-2 evaluation than in the present study. Differences such as those in the present study could be expected also with other tumor markers in cervical cancer and in other cancer types with histological subtypes. The number of adenocarcinomas was small, but in contrast to squamous cell carcinoma there was no evidence that any of the tumor makers could be useful for prognosis prediction even if the study population had been larger and the p-values in comparisons were generally high.
The present study highlighted the importance of not copying uncritically the choice of tumor markers when assessing carcinomas with different histological diagnoses even in the same cancer type. The differing expression of tumor markers might indicate different impact on the carcinogenesis in different cancer types. A mixture of histological subtypes in the evaluation of prognostic prediction could therefore lead to wrong conclusions.
- Received January 12, 2009.
- Revision received March 5, 2009.
- Accepted April 2, 2009.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
