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Oulun yliopiston väitöskirjat

LUNG ADENOCARCINOMA, ACTA UNIVERSITATIS OULUENSIS D Medica 1425

ISBN-13:	978-952-62-1620-1
Kieli:	englanti
Kustantaja:	Oulun yliopisto
Oppiaine:	Lääketiede
Painos:	Osajulkaisuväitöskirjan yhteenveto-osa
Painosvuosi:	2017
Sijainti:	Print Tietotalo
Sivumäärä:	128
Tekijät:	MÄKINEN JOHANNA

24.00 €

Pulmonary adenocarcinoma is the most common and most heterogeneous form of lung cancer, and its histological and biological diversity is well recognized. On its publication in 2011, the IASLC/ ATS/ERS lung adenocarcinoma classification drew attention to the prognostic value of adenocarcinoma subtypes, and it has been anticipated to provide a novel architecture based grading system. The prognostic role of other tumor-associated features in lung adenocarcinoma is less established. MUC1 overexpression has been demonstrated in many carcinomas, and in lung adenocarcinoma, depolarized MUC1 expression has been associated with poor outcome. The role of MUC4 in lung cancer, however, is somewhat conflicting. Moreover, there is no published data on either MUC1 or MUC4 expression with regard to the different subtypes of lung adenocarcinoma. This study aimed to investigate the correlation between the IASLC/ATS/ERS classification, prognosis, and clinical characteristics in a series of 112 surgically resected lung adenocarcinoma patients. The analysis of tumor architecture aimed also at the discovery of new morphological biomarkers for lung cancer. Additionally, the study focused on the expression of MUC1, MUC4, and EGFR in lung adenocarcinoma, evaluating their relationship with tumor architecture, patient outcome, and smoking. The study applied the methods of light microscopy, immunohistochemistry, and cell culture with experimental cigarette smoke exposure combined with real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunoelectron microscopy. The study demonstrated that the prognostic value of the current adenocarcinoma classification is not limited to predominant growth patterns as a more favorable clinical outcome was associated with minor lepidic pattern. Significant associations were observed between adenocarcinoma subtypes and smoking history. Classic histological features of malignancy correlated with tumor architecture and survival, further confirming the prognostic value of semiquantitative growth pattern analysis and identifying potential prognostic biomarkers such as mitotic activity and tumor necrosis. Depolarized MUC1 expression correlated with histology and patient outcome, and moreover, with smoking both in vivo and in vitro, suggesting a pathogenetic relationship between cigarette smoke exposure and MUC1 in lung adenocarcinoma.

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