Prognostic index expression of cyclin-D1, cerbB-2 and VEGF: metastases vs corresponding primary cancers and metastatic vs non-metastatic adenocarcinomas.
The prognostic relevance of different molecular markers in lung cancer is a crucial issue still worth investigating, and the specimens collected and analyzed represent a valuable source of material. Cyclin-D1, c-erbB-2 and vascular endothelial growth factor (VEGF) have shown to be promising as prognosticators in human cancer. In this study, we sought to examine the importance of Cyclin-D1, c-erbB-2 and VEGF, and to study the quantitative relationship among these factors and disease progression in metastases vs corresponding primary cancer, and metastatic vs non metastatic cancers.



We used immunohistochemistry and morphometric analysis to evaluate the amount of tumour staining for Cyclin-D1, c-erbB-2 and VEGF in 52 patients with surgically excised adenocarcinoma of the lung, and the outcome for our study was survival time until death from hematogenic metastases.



Metastasis presented lower c-erbB-2 expression than corresponding primary cancers (p=0.02). Cyclin-D1 and VEGF expression were also lower in metastases than in corresponding primary cancers, but this difference did not achieve statistical significance. Non-metastatic cancers also presented significantly lower Cyclin-D1 and c-erbB-2 expression than metastatic cancers (p<0.01 and p<0.01, respectively). Equally significant was the difference between higher c-erbB-2 expression by metastatic cancers compared to non-metastatic cancers (p=0.02). Considering survival in Kaplan-Maier analysis, Cyclin-D1 (p=0.04), c-erbB-2 (p=0.04) and VEGF (p<0.01) were important predictors of survival in metastatic cancers.



Different tumour cell profiles in metastases, corresponding primary cancers, and non-metastatic cancers were found, thus suggesting that different cell clones control the invasive and non-invasive behaviour of the cancers. The fact that cancers with higher indexes of Cyclin-D1, cerbB-2 and VEGF expression have the capacity to metastasize offers us the potential to guide the use of adjuvant chemotherapy in patients likely to fail treatment after surgical excision of cancers.
Parra
Edwin Roger
ER
Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, Brazil. erparra20003@yahoo.com.br
Park
Ji Young
JY
Saito
Dalva Midori
DM
Takagaki
Teresa Yae
TY
Rodrigues
Olavo Ribeiro
OR
Capelozzi
Vera Luiza
VL
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D056741:Cyclin D; D016213:Cyclins; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human