Non-mucinous and mucinous subtypes of adenocarcinoma with bronchioloalveolar carcinoma features differ by biomarker expression and in the response to gefitinib.
There is no optimal established therapy for treating advanced or recurrent adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC), and it remains unclear whether chemotherapy achieves therapeutic results comparable to those seen in the more common non-small lung carcinoma subtypes. In order to improve the decisions made during the treatment of advanced ADC-BAC, we attempted to better characterize the mucinous and non-mucinous ADC-BAC subtypes. Fifty pathological samples were obtained from 62 patients included in a multicenter prospective phase II trial (IFCT0401) conducted to evaluate gefitinib as a first-line therapy for non-resectable ADC-BAC. These samples were centrally reviewed and re-classified as non-mucinous (n=25) or mucinous (n=25) subtypes. We demonstrated that demographic data, clinical characteristics and stage at presentation (extrathoracic versus lung metastasis, as well as TNM staging) did not distinguish between the two subtypes. In contrast, three biological markers (PAS staining, TTF-1 expression and EGFR genomic gain combined with mutation analysis) enabled us to independently segregate all but 2 of the 50 patients into the mucinous and non-mucinous ADC-BAC subtypes. Finally, only mucinous tumors appeared to be resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Additional prospective studies are required to better approach therapeutic strategy in mucinous tumors, which are a distinct entity from non-mucinous tumors.
Wislez
Marie
M
Service de Pneumologie et de Réanimation, AP-HP, Hôpital Tenon, Paris, France. marie.wislez@tnn.aphp.fr
Antoine
Martine
M
Baudrin
Laurence
L
Poulot
Virginie
V
Neuville
Agnes
A
Pradere
Maryvonne
M
Longchampt
Elisabeth
E
Isaac-Sibille
Sylvie
S
Lebitasy
Marie-Paule
MP
Cadranel
Jacques
J
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use; D014157:Transcription Factors
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011799:Quinazolines; C504003:TTF1 protein, human; D014157:Transcription Factors; D066246:ErbB Receptors; D000077156:Gefitinib