Nuclear and environment morphometric profile in tumor size and nodal metastasis of resected typical pulmonary carcinoid.
As the biologic behavior in lung tumors with neuroendocrine differentiation is highly dependent on cell death (apoptosis) and extracellular matrix invasion, Bcl2 and extracellular matrix density have been targeted as potentially useful tumor markers. In this study, we sought to validate the importance of Bcl2 and ECM density and to study the relationships of Bcl2 and ECM density with clinical factors and other tumor or stromal markers. We examined Bcl2 and several other markers in tumor tissues from 55 patients with surgically excised pulmonary typical carcinoid. We used histochemistry, immunohistochemistry, and morphometry to evaluate the amount of tumor staining for Bcl2 and ECM; the surrogate markers for aggressive potential for our study were tumor size and lymph node metastasis determined at diagnosis. Multivariate logistic model analysis demonstrated that after surgical excision control, tumor size was significantly related to nodal metastasis (P = 0.01), but quantitative staining of the tumor for Bcl2 and ECM added prognostic information and was as strongly prognostic as tumor size (P<0.01). Cutpoints at the median staining of 3.1% and 9.8 microm2 for Bcl2 and ECM, respectively, divided patients into two groups with distinctive risk for nodal metastasis. Those with Bcl2 > 3.1% and ECM <9.8 microm2 had high risk for nodal metastasis. We concluded that tumor staining for Bcl2 and ECM in resected PTC is strongly related to tumor size and nodal metastasis. Patients with > 3.1% and <9.8 microm2 staining in their tumors comprise a subset with a high hazard for nodal metastasis and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.
Department of Thoracic Surgery of Hospital das Clinicas, University of São Paulo, Brazil.
João Carlos
JC
das Neves Pereira
Alecsander Guilharman Pereira
AG
da Silva
Fabiana
F
Soares
Alexandre Muxfeldt
AM
Ab'Saber
Aurelino
A
Schmidt
Olavo Ribeiro
OR
Rodrigues
Ana
A
Garippo
Marisa
M
Capelozzi
José Ribas Milanez
JR
de Campos
Tereza
T
Takagaki
Fábio Biscegli
FB
Jatene
Sandro
S
Martins
Vera Luiza
VL
Capelozzi
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D002467:Cell Nucleus / Q000473:pathology*; D002648:Child; D003094:Collagen / Q000378:metabolism; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013903:Thoracic Surgery; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D003094:Collagen