Prognostic factors in resected non-small cell lung cancer: an immunohistochemical study of 39 cases

doi:10.1016/S0169-5002(96)00610-1

Lung Cancer

Volume 16, Issue 1, December 1996, Pages 35-45

https://doi.org/10.1016/S0169-5002(96)00610-1 Get rights and content

Abstract

Non-small cell lung carcinoma (NSCLC) is a histologically heterogeneous collection of tumours with variable clinical behaviour. Performance status, tumour stage and histological type have important prognostic implications, but the clinical outcome in an individual patient remains unpredictable. In search of other prognostic factors we studied the expression of several immunohistochemical markers in NSCLC, resected with curative intent. Tumour samples of 19 patients with a postoperative disease-free survival of at least 5 years and those of 20 patients who died of tumour recurrence within 2 years after resection were selected for this study. The populations were matched for age, sex and tumour stage. We investigated the expression of markers for neuroendocrine differentiation, cell adhesion and cell cycle regulation in both populations. None of the investigated immunohistochemical markers distinguished between long- and short- term survivors of resected NSCLC. In stage 1 tumours expression of embryonal NCAM was observed more often in the short survival group (P = 0.026) and in stage 3a EGF-r expression was associated with the long survival group (P = 0.047). However, these findings remained to be confirmed. Expression of Rb, NCAM and embryonal NCAM was not detected in adenocarcinomas, whereas T-Ag and chromogranin A immunoreactivity was absent from squamous cell carcinomas.

References (33)

SA Rosenthal et al.
The significance of histology in non-small cell lung cancer
Cancer Treat Rev
(1990)
B Passlick et al.
Immunohistochemical detection of P53 protein is not associated with a poor prognosis in non-small-cell lung cancer
J Thorac Cardiovasc Surg
(1995)
M Tateishi et al.
Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma
Surg Oncol
(1994)
G Fontanini et al.
Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype
Eur J Cancer
(1995)
DP Carbone et al.
P53 immunostaining positivity is associated with reduced survival and is imperfectly correlated with gene mutations in resected non-small cell lung cancer. A preliminary report of LCSG 871
Chest
(1994)
RE Kibbelaar et al.
Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma
Eur J Cancer
(1991)
HB Kwa et al.
The prognostic value of NCAM, P53 and Cyclin D1 in resected non-small cell lung cancer
Lung Cancer
(1996)
BG Skov et al.
Prognostic significance of histologic demonstration of chromogranin A and neuron specific enolase in pulmonary adenocarcinoma
Ann Oncol
(1991)
RI Linnoila et al.
Impact of neuroendocrine differentiation in non-small cell lung cancer. The LCSG experience
Chest
(1994)
World Health Organization

P Hermanek et al.

Lung and pleural tumours

GE Richardson et al.

The biology of lung cancer

Semin Oncol

(1993)

M Ebina et al.

Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer

Cancer Res

(1994)

DH Harpole et al.

A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histology, and oncoprotein expression

Cancer Res

(1995)

B Top et al.

P53 gene mutation and protein accumulation in human non small cell lung cancer

Int J Cancer (Pred Oncol)

(1995)

M Volm et al.

Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations

Anticancer Res

(1992)

Cited by (22)

Neuroendocrine Lesions of the Lung
2011, Practical Pulmonary Pathology E-Book: A Diagnostic Approach, Second Edition
Neuroendocrine Lesions of the Lung
2011, Practical Pulmonary Pathology: A Diagnostic Approach A Volume in the Pattern Recognition Series
Lung tumours with neuroendocrine differentiation
2009, European Journal of Cancer
Citation Excerpt :
It is seen most often in adenocarcinomas. The data do not show any consistent clinical significance either with regard to prognosis or responsiveness to chemotherapy [89,109,109–125]. LCNEC patients have an aggressive clinical course with overall 5-year survivals ranging from 15–57%.
Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers
2006, Lung Cancer
Apoptosis related proteins in early staged NSCLC seem to have prognostic value. We studied the value of a combination of eight of those proteins in advanced NSCLC.
Bronchoscopically procured tumor biopsies of NSCLC patients were stained immunohistochemically and rated for expression of eight different cellular proteins. Patients were treated with 60 Gy radiotherapy with or without carboplatin as radiosensitizer.
Apoptotic proteins in tumors that showed positive staining were the highest for Bax (99%), Fas (92%), FasL (87%), Rb (87%), p21(WAF1) (73%), and p53 (70%), and the lowest for c-myc (58%) and Bcl-2 (58%). In the Cox regression analysis Bcl-2 positivity (RR = 0.61, 95% CI, 0.37–0.98, p = 0.04) was predictive for overall survival. Only Bcl-2 staining percentage (RR₁₀ (RR associated with an increase in stained cells of 10%) = 0.93, 95% CI, 0.89–0.99), p53 (RR₁₀ = 0.94, 95% CI, 0.89–0.99) and FasL (RR₁₀ = 0.92, 95% CI, 0.86–0.99) were predictive for a longer progression-free survival. No specific constellation of apoptotic proteins was associated with tumor response.
Bcl-2 expression in tumor tissue of patients with unresectable NSCLC predicts a better overall survival, while Bcl-2, p53, and FasL expressions predict for a longer progression-free survival.
The role of apoptosis-related genes in non-small-cell lung cancer
2002, Clinical Lung Cancer
Both intrinsic and acquired resistance to chemotherapeutic drugs are major obstacles in the treatment of non—small-cell lung cancer. Apart from classical drug resistance mechanisms, the failure of tumor cells to undergo apoptosis also plays an important role in drug resistance. Mutations and defects in the apoptotic pathway are, therefore, additional factors that determine drug resistance. The tumor suppressor gene p53, the retinoblastoma gene, and the bcl-2 family members are important factors in this pathway. Recently much attention has been drawn to different apoptotic pathways induced by naturally occurring death receptor ligands (such as tumor necrosis factor, Fas ligand, and tumor necrosis factor—related apoptosis-inducing ligand) or induced by drugs that affect the downstream pathway from the epidermal growth factor receptor. Insight regarding the proteins that determine sensitivity for chemotherapeutic drugs could provide new targets for cancer treatment, which may help to at least partly overcome drug resistance in non—smallcell lung cancer.
Characteristics of long-term survivors of untreated lung cancer
2002, Lung Cancer
Non-small cell lung cancer (NSCLC) is a malignant tumor with poor prognosis. Although the prognostic variables determining short-term survival have been well described, relatively little attention has been paid to factors associated with long-term survival. In search of these factors we studied the expression of several molecular markers in NSCLC. Only tumor samples of patients with squamous cell carcinomas and stage III tumors with a postoperative survival of at least 5 years and those of patients who died within 2 years after resection were selected for this study. The expression of several parameters including oncogene and suppressor gene products, proliferative, apoptotic, angiogenic and resistance-related factors were investigated and the differences in these two extreme populations were determined by the Wilcoxon rank sum test. Factors involved in proliferation (ras, fos, erbB-1, jun, cyclin A) were downregulated whereas factors involved in apoptosis (p53, bcl-2, CD95) were upregulated in the long survival group. Direct measurement of parameters of proliferation (cell cycle analysis by flow cytometry, PCNA index) revealed a lower proliferative activity in tumors of the long survivors compared to short survivors. In conclusion, tumors of the long survival group are characterized by a downregulation of factors involved in proliferation and an upregulation of factors involved in apoptosis. These tumors may grow more slowly and this may influence long-term survival of patients with NSCLC.

View all citing articles on Scopus

View full text

Feature articlePrognostic factors in resected non-small cell lung cancer: an immunohistochemical study of 39 cases

Abstract

Cancer Treat Rev

J Thorac Cardiovasc Surg

Surg Oncol

Eur J Cancer

Chest

Eur J Cancer

Lung Cancer

Ann Oncol

Chest

Lung and pleural tumours

The biology of lung cancer

Semin Oncol

Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer

Cancer Res

A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histology, and oncoprotein expression

Cancer Res

P53 gene mutation and protein accumulation in human non small cell lung cancer

Int J Cancer (Pred Oncol)

Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations

Anticancer Res

Feature article
Prognostic factors in resected non-small cell lung cancer: an immunohistochemical study of 39 cases