Atypical adenomatous hyperplasia (AAH) has been recently defined by WHO as a small lesion, non exceeding the 5 mm in major axis, composed of slightly enlarged alveolar septa lined by pneumocytes with plump, atypical nuclei. AAH is frequently found in tissue surrounding lung adenocarcinoma and it is considered a precursor of this subtype of lung cancer by many Authors. However, little is known about the genetic relationship between adenocarcinoma and the associated foci of AAH. In particular , it is not clear if multiple foci of AAH and of adenocarcinoma in the same patients are clonally related each other or represent independent neoplastic foci. To clarify the relationship between AAH and the associated cancer, we studied 23 foci of AAH and 18 adenocarcinomas from 16 patients. Cytologic atypia in each focus of AAH has been graded as slight, moderate or severe. In addition, by microdissection tecnique we obtained DNA from each focus of AAH, each focus of cancer, normal pneumocytes and normal lymphocytes. Therefore we evaluated the genetic distance between AAH and cancer in the same patients, using LOH analysis for 7 microsatellites (D3S1478, D3S1300, D9S942, D17S261, D17S250, D18S46, D19S246) and by direct sequencing of the D-loop region of Mithocondrial DNA. We found that the most frequent LOH in AAH were in D3S1478 and D3S1300 (close to FHIT gene). However, our results indicate that in AAH there is no significant correlation between the degree of cytologic atypia and LOH. On the contrary the frequency of LOH seems to correlate with the degree of differentiation in foci of carcinoma, being rarely present in well differentiated bronchioloalveolar carcinomas and frequent in poorly differentiated adenocarcinomas. Finally, in our series the pattern of LOH in AAH foci was different from the pattern of LOH in the cancer from the same patient, indicating that AAH and the associated cancer are genetically indipendent. These results were confirmed also by the phylogenetic trees obtained by direct sequencing of mitochondrial DNA.
S.Asioli, L.Morandi, A.Cavazza, A.Pession, S.Damiani (2004). Atypical hyperplasia associated with adenocarcinoma of the lung: a molecular study. TRIESTE : sine nomine.
Atypical hyperplasia associated with adenocarcinoma of the lung: a molecular study
ASIOLI, SOFIA;MORANDI, LUCA;PESSION, ANNALISA;DAMIANI, STEFANIA
2004
Abstract
Atypical adenomatous hyperplasia (AAH) has been recently defined by WHO as a small lesion, non exceeding the 5 mm in major axis, composed of slightly enlarged alveolar septa lined by pneumocytes with plump, atypical nuclei. AAH is frequently found in tissue surrounding lung adenocarcinoma and it is considered a precursor of this subtype of lung cancer by many Authors. However, little is known about the genetic relationship between adenocarcinoma and the associated foci of AAH. In particular , it is not clear if multiple foci of AAH and of adenocarcinoma in the same patients are clonally related each other or represent independent neoplastic foci. To clarify the relationship between AAH and the associated cancer, we studied 23 foci of AAH and 18 adenocarcinomas from 16 patients. Cytologic atypia in each focus of AAH has been graded as slight, moderate or severe. In addition, by microdissection tecnique we obtained DNA from each focus of AAH, each focus of cancer, normal pneumocytes and normal lymphocytes. Therefore we evaluated the genetic distance between AAH and cancer in the same patients, using LOH analysis for 7 microsatellites (D3S1478, D3S1300, D9S942, D17S261, D17S250, D18S46, D19S246) and by direct sequencing of the D-loop region of Mithocondrial DNA. We found that the most frequent LOH in AAH were in D3S1478 and D3S1300 (close to FHIT gene). However, our results indicate that in AAH there is no significant correlation between the degree of cytologic atypia and LOH. On the contrary the frequency of LOH seems to correlate with the degree of differentiation in foci of carcinoma, being rarely present in well differentiated bronchioloalveolar carcinomas and frequent in poorly differentiated adenocarcinomas. Finally, in our series the pattern of LOH in AAH foci was different from the pattern of LOH in the cancer from the same patient, indicating that AAH and the associated cancer are genetically indipendent. These results were confirmed also by the phylogenetic trees obtained by direct sequencing of mitochondrial DNA.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
