Elsevier

Lung Cancer

Volume 44, Issue 3, June 2004, Pages 295-301
Lung Cancer

Correlation of different markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the diagnostic biopsies and the corresponding resected tumors in non-small cell lung cancer

https://doi.org/10.1016/j.lungcan.2003.12.009Get rights and content

Abstract

Substaging using molecular markers has been proposed to try to identify prognostic factors allowing to define groups of patients with lung cancer for whom specific therapy might be of benefit. The pre-operative assessment of these markers seems to be important specially in case of neoadjuvant chemotherapy.

The aim of our study was to compare the expression of two potential prognostic factors (p53 and Ki-67) and two potential therapeutic targets (EGF-R and c-erbB-2) assessed on biopsy samples (B) of non-small cell lung cancer (NSCLC) with that of the corresponding resected tumor (RT). The expression of these biological markers was evaluated by immunohistochemistry on B and on the paired RT in 28 patients.

The mean percentage of p53 positive cells was 28% in RT and 38% in B with 81% CR between B and RT and 19% FP on B. Considering RT results as standard, the positive (PPV) and negative predictive value (NPV) of the B were, respectively, 74 and 100%. The mean percentage of EGF-R positive cells was 11% in RT and 28% in B. With a cut-off of 1%, we found 85% concordant results (CR) between B and RT, 4% false negative (FN) and 11% false positive (FP) on B. The PPV and NPV values of the B were, respectively, 80 and 92%. The 8% B and 19% RT were considered as positive for c-erbB-2. We found 15% FN and 4% FP on B with 81% CR between B and RT for c-erbB-2. The NPV of the B was 83%. The mean percentage of Ki-67 positive cells was 32% in RT and 14% in B. We found 82% CR between B and RT, 14% FN and 4% FP on B. The PPV of the B was 96%.

In conclusion, biopsies may provide reliable information about p53, EGF-R, c-erbB-2 and Ki-67 in lung carcinoma and could help to elaborate a therapeutic strategy.

Introduction

Lung cancer is the most common cause of death by malignancy in industrialized countries [1]. Less than one-third of the patients can be surgically treated for localized disease with curative intent. The majority of the patients are in an advanced stage at the time of diagnosis and the treatment consists in chemo- and/or radiotherapy. Unfortunately, the efficacy of these therapies is modest. Increased attention has then turned upon new biological parameters [2], [3] in order to try to identify prognostic factors allowing to define groups of patients for whom specific therapy might be of benefit. Substaging using molecular markers has been proposed [4] although their role as prognostic factor remains unclear. In addition, new therapeutic agents targeting other proliferative pathways, are under investigation and require, as a prerequisite, tumor characterization of these biological and/or molecular factors.

In case of resectable disease, biological parameters have been mainly evaluated so far by immunohistochemistry on paraffin-embedded tissues obtained at the time of the surgical resection of the primary tumor. A new approach in the treatment of resectable non-small cell lung cancer (NSCLC), however, consists to administer neoadjuvant chemotherapy [5]. As a corollary, evaluation of markers on the resected tumor may no longer be possible and may also be altered by the induction therapy. Whenever the lung cancer is not resectable, evaluation of markers should also be limited to small biopsy specimens of tissues. Consequently, it could be of particular interest to assess whether the expression of markers assessed on small biopsy specimens obtained during a non-surgical procedure (e.g. bronchoscopy) are effectively a good representation of the tumor. Few studies have been published concerning the evaluation of biological markers on pre-operative biopsies of carcinoma of the lung [6].

With this in mind, we have compared the expression of two potential prognostic factors (p53 and Ki-67) and two others potential therapeutic targets (EGF-R and c-erbB-2) assessed by immunohistochemistry on biopsy samples obtained during bronchoscopy with that of the corresponding resected NSCLC.

Section snippets

Study population

We selected all the patients surgically resected for a NSCLC and for whom a pre-operative bronchoscopic biopsy confirmed the diagnosis of NSCLC in our institution. From November 1992 to July 2000, 129 consecutive patients were treated by lobectomy or pneumonectomy for lung carcinoma in our Department of Thoracic Surgery. Sixty-eight of these cases had a pre-operative diagnosis of lung cancer. In 16 cases, pre-operative diagnosis was made on cytology specimens and three patients received

Results

Among the 49 eligible patients, 26, 27, 26, and 28 were assessable both on the tumor and on biopsy for p53, EGF-R, c-erbB-2 and Ki-67, respectively, because we did not have enough tissue sample available for the immunostaining. They included 22 males and 6 females with a median age of 60 years (ranging from 38 to 78 years). Histology was squamous cell carcinoma in 15, adenocarcinoma in 12 and large cell neuroendocrine tumor in 1.

The results on resected tumors is considered as the gold standard.

Discussion

Usually, biological parameters in lung cancer are immunohistochemically evaluated on paraffin-embedded tissues obtained at the time of the surgical resection of the primary tumor. The aim of our study was to compare the immunohistochemical expression of p53, EGF-R, c-erbB-2 and Ki-67 on paired biopsy and surgical samples to evaluate if the results obtained are similar. We observed about 80% concordant results when comparing biopsies and surgical specimens with low false negative and false

Acknowledgements

This research was supported by a FNRS-Télévie grant (no. 7.4512.98); Anne-Pascale Meert is a FNRS research fellow (no. 3.4579.02). This research was also supported by “Les Amis de l’Institut Bordet” (Dr. Benoit Martin and our lab technician Marie Schoonakers).

References (16)

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