Abstract

The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. Retrospective pilot study of the surgically treated non-small cell lung cancer biopsy specimen, paraffin embedded, used immunohistochemical method to demonstrate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2. Protein quantification was performed by the semi-quantitative method. Achieved results were correlated with classical clinico-pathological parameters, like tumor size, histological type, differentiation level, presence of vascular invasion and metastasis in regional lymph nodes. Out of 14 cases of non-small cell lung cancer, squamous cell carcinoma was found in 7 patients, giant cell carcinoma in 3, adenocarcinoma in 2, and 1 case of pleomorphic and mucoepidermoid carcinoma. Expression of cyclin D1 was not found, while expression of HER-2 and bcl-2 protein was established in one cases each. p53 expression was noted in 8 cases (57,1%). Statistically positive significant correlation (p<0,05) was found among: presence of lymphovascular invasion to tumor tissue and appearance of nodal metastasis; proliferation Ki-67 index and level of tumor differentiation, i.e. size of tumor. Other investigated parameters showed no significant statistically dependence. p53 expression was not correlated to any of the investigated parameters what might imply the possibility that there is an independent pathway of this protein expression. Negative expression of bcl-2 protein points out to possibility that it is not included into process of tumor apoptosis, as well as that proteins cyclin D1 and HER-2 are not included into processes of the tumor genesis. Since the proliferative activity of the tumor, measured by the expression of Ki-67, is correlated to the gradus and size of the tumor mass, Ki-67 protein can be of a prognostic value to determine biological potential of non-small cell lung cancer.

Highlights

  • Non-small cell lung cancer up to date has been a subject to many epidemiological, etiological, pathohistological and other aspects of investigation

  • In a pilot study of cases of non-small cell lung cancer expression of cyclin D, p, bcl, Ki- and HER- were investigated, which are correlated with classical clinical-pathological parameters, like size and level of differentiation of tumor, presence of lymphovascular invasion in cancer cells of tumor tissue and surrounding tissue, and presence of metastasis in regional lymph nodes

  • Positive significant correlation (p

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Summary

Introduction

Non-small cell lung cancer up to date has been a subject to many epidemiological, etiological, pathohistological and other aspects of investigation All these investigation demonstrated that in prognosis of this cancer type classical clinico-pathological parameters are no longer sufficient since the proteins, which are products of different types of oncogenes and suppressor genes, dictate biological behavior of neoplasm ( - ). Bcl- oncogene and p suppressor gene are included in that manner in process of cell death and tumor proliferation. Overexpression of HER- in membranes of tumor cells is a part of malignant transformation and tumor progression processes ( - ) Activation of this receptor stimulates signal transduction what leads to increased level of intracellular calcium and increased plasma membrane potential what has mitogen effect ( ). Hypothesis is that distribution and intensity of abovementioned protein can be important factor of differentiation and metastatic potential, and can be of help in prognosis of non-small cell lung cancers

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