MOLECULAR PATHOLOGY OF LUNG ADENOCARCINOMA

POPESCU IULIAN PhD, MD, Clinical Department of Radio-Biology at the Fundeni Clinical Institute in Bucharest

e-mail: popdociul@yahoo.com

              ALINA HALPERN PhD, SF.ŞTEFAN Hospital  Bucharest

INTRODUCTION.

Lung Cancer (C:P.) develops through the accumulation of multiple alterations molecular, genetic and epigenetic causing the aberrant gene functioning. Aneusomya (the presence of an abnormal number of chromosomes) is associated with lung cancer. It has not been defined yet whether aneumosomya also exists in pre-neoplastic lesions (3)). Smoking is an important etiologic factor. The tobacco components facilitates tumorigenesis through genotoxic efects and by modeling the signaling pathways.
            Lung cancer still remains a serious illness, the number of deaths exceeding deaths following the cancer of prostate, breast and colon taken together. The five-year survival remained 15 %, instead in the other locations increased up to 64 % of colon cancer , 88 % breast cancer and 99 % prostate cancer  (4.1)

MOLECULAR PATHOLOGY OF THE SQUAMOUS FORM OF NON-SMALL CELL LUNG CANCER

 POPESCU IULIAN PhD, MD, Clinical Department of Radio-Biology at the Fundeni Clinical Institute in Bucharest

e-mail: popdociul@yahoo.com

              ALINA HALPERN PhD, SF.ŞTEFAN Hospital  Bucharest

INTRODUCTION

Study of the molecular pathology of lung cancer (LC) has contributed and is further contributing to a more deepened knowledge of pre-neoplastic lesions, of carcinogenesis process, of metastatic invasion and disseminations. By simultaneously highlighting multiple markers the early diagnosis becomes possible in the targeted treatment of LC. So far the LC treatment was a uniform treatment for a heterogeneous disease. These cumulated data give hope for the increase of survival rate, which currently is one of the lowest

LARGE CELL LUNG CANCER. ISSUES OF MOLECULAR PATHOLOGY

POPESCU IULIAN PhD, MD, Clinical Department of Radio-Biology at the Fundeni Clinical Institute in Bucharest

e-mail: popdociul@yahoo.com

             ALINA HALPERN PhD, SF.ŞTEFAN Hospital  Bucharest

Classification of Lung Cancer (LC) is primarily performed in morphological terms and in particular through immunohistochemical methods.

Large cell carcinomas are a distinct group of tumors within the non-small cell lung cancer.

The diagnosis of large cell lung cancer - until now - is made by the exclusion of other forms of lung cancer (LC)

Wtihin large cell lung cancer it is observed - at ultrastructural level - conformations of squamous or glandular differentiation (1,2,3)

Large cell lung cancer has a number of sub-categories:

SMALL CELL LUNG CANCER

Molecular Pathology OF THE

SMALL CELL LUNG CANCER

INTRODUCTION

The small cell lung cancer is an epithelial malignant tumor made up of small cells, with cytoplasm poor, marginal, with fine, granular appearance and lack of nucleoli. It has a high rate of mitosis and extensive necrosis. It differs through a very high nuclear-cytoplasmic ratio (1).

So far no precursors are not known, as well as for the lung cancer with neuroendocrine cells. The diffuse neuroendocrine hyperplasia is not considered pre-neoplastic lesion (1).

The lung neuroendocrine neoplasms are a wide range of entities phenotypic, biologically distinct, starting from the typical and atypical carcinoids up to small cell lung cancer and lung cancer with neuroendocrine cells.

The neuroendocrine appearance is highlighted through immuno-histochemistry and electron microscopy (2).

Small cell lung cancer forms simultaneously part of the neuroendocrine tumors with neuroendocrine cell

THE MECHANISM OF ACTION AND MECHANISM OF RESISTENCE OCCURENCE IN THE TREATMENT WITH TYROSINE-KINASE INHIBITORS

IULIAN POPESCU, PhD, MD

The Clinical Department of Radiobiology from the Fundeni Clinical Institute,

e-mail: popdociul@yahoo.com

Alina Halpern, PhD,  "Sf. Stefan" Hospital, Bucharest

ABSTRACT

Since 2000 a new era has begun in the treatment of lung adeno-carcinoma (ADC), which will improve, diversify, enrich the chemotherapy treatment of lung cancer (PA) which becomes the targeted treatment for a heterogeneous disease. The tyrosine-kinase inhibitors (ITK) have effect only upon ADC with EGFR mutations.

The most frequent mutations are at the level of the 19th exon  through deletion and at the level of the 21st exon  through punctiform mutations (T858R)

The EGFR and Kopi mutations, after the stimulation of ligands, undergo a homo or heterodimerization, leading to the autophosphorylation of the ATP / EGFR group, which in turn activate the pathways: PI3K/AKT, JAK/STAT and Ras/MAPK which further lead to cellular growth, survival and proliferation. The ITK blocks the ATP- EGFR phosphorylation, leading to the increase of cellular apoptosis. But after a period

THE EPITHELIAL MESENCHYMAL TRANSITION - MAIN FACTORS AND ITS INSTALLATION MECHANISM

POPESCU IULIAN, PhD, MD,

The Radiobiology Department of the Clinical Institute in Fundeni Bucharest

E-mail: popdociul@yahoo.com

ALINA HALPERN, PhD "St. Stefan" Hospital, Bucharest

ABSTRACT

The metastatic progression is responsible for most deaths from cancer in humans. For achieving this it is necessary to convert the epithelial phenotype of cancer cells into the mesenchymal phenotype that favours metastasis. This transformation, which is transient, is called Epithelial-Mesenchymal Transition (EMT).

The epithelial cancerous cells are characterized by immobility, apical-basal polarity, strong junctions of desmozomes, an interaction between the cell and extracellular matrix and an increased expression of cell adhesion markers, where E-cadherin plays the main role.

The mesenchymal cell is mobile, multi-polar, fusiform aspect, does not make strong cell-cell contacts, it can invade and express multiple markers, which confers these properties.

The TEM process is a complex mechanism involving changes in the expression, distribution and /or function of several proteins. Among the main factors, we distinguish:

THE CANCER STEM CELLS AND LUNG CANCER

POPESCU IULIAN PhD,MD, Clinical Department of Radio-Biology at the Fundeni Clinical Institute in Bucharest

e-mail popdociul @yahoo.com

Dr. ALINA HALPERN PhD, SF.ŞTEFAN Hospital  Bucharest

It is well recognized that lung localization of the cancer is one with the weakest therapeutic results, with all scientific conquests as concerns the therapies obtained from 1950 until today. Surviving more than 5 years is below 15%, compared to results from other localizations (99% in prostate cancer, 86% in breast cancer, 66% for colon cancer, 30% in ENT sphere cancer). In lung cancer encouraging results have been obtained in the possibility of increasing the survival time without relapse (disease free survival), but not also concerning the overall survival. The main task in the treatment of lung cancer remains the prolongation of overall survival and