Fylenko B. Pathomorphological features of well differentiated squamous cell lung cancer

The thesis considers the solution for optimization of pathomorphological diagnosis and grounding of the prognostic criteria by defining the relationship between the histostructural features of keratinizing squamous cell lung cancer and the expression of the molecular genetic markers of proliferation, apoptosis, differentiation and adhesion. The clinicomorphological, immunohistochemical and histological studies have been based on the 54 cases of the postoperative material. It has been found that the tumor size, occurrence of the secondary changes in carcinoma (cancer cavern) and inflammatory infiltration in the surrounding tissues are not the reliable prognostic criteria in well differentiated squamous cell lung cancer. It has been determined that sudanophilic, PAS- and thionine-positive keratin pearls, characterized by the different degree of differentiation, are formed in the keratinizing squamous cell lung cancer. The features of expression of molecular biological markers of the cellular proliferation, differentiation, adhesion and apoptosis, as well as their role in the morphogenesis of keratinizing squamous cell lung cancer have been immunohistochemically established. The comparison of the morphological, morphometric and molecular-genetic features of well differentiated squamous cell lung cancer provided with clarification of the mechanisms of formation of various histochemical types of "keratin pearls" and grounding of the morphological prognostic criteria. The scientific data on the prognostic value of the markers of proliferation (Ki-67 and cyclin D1), cytodifferentiation (Е-cadherin and CK HMW) and regulators of apoptosis (р53 and Bcl-2) have been supplemented. It has been established that unfavorable prognostic morphological criteria are the predominance of tumor complexes with lipid-positive keratin pearls that is associated with the high index of proliferation, р53 and Bcl-2 expression and low response to Е-cadherin and CK HMW, predominance of the parenchymatous component over the stromal one. The resulting data contribute to the more profound understanding of morphological diagnosis and prognosis of the disease.