Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer

Abstract

Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (Po0.001), also when the surrounding invasive carcinoma was unreactive. Fascin immunoreactivity correlated with high tumour grade (P ¼ 0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P ¼ 0.021). Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for fascin than invasive tumours (P ¼ 0.005). Contralateral thoracic or distant metastases were associated significantly with diffuse (460% immunoreactive tumour cells) fascin expression in adenocarcinomas (P ¼ 0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P ¼ 0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (460% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P ¼ 0.006 for adenocarcinomas and P ¼ 0.026 for squamous cell carcinomas), even after multivariate analysis (P ¼ 0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.

Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

“…Fascin immunoreactivity was not associated with the tumour proliferation fraction as assessed by the Ki-67-labelling index, at variance with previous studies of lung and stomach cancers and also of colonic cell cultures (Jawhari et al, 2003;Pelosi et al, 2003b;Hashimoto et al, 2004). In a recent work on CRC, similar to the current one, comparing fascin expression with Ki-67 immunostaining, a lack of direct association between the two markers was noted, indicating that the fascin upregulation do not correlate positively with cell proliferation (Hashimoto et al, 2006).…”

“…The main results are that fascin is upregulated in most colonic carcinomas, correlating with a higher tumour grade, right tumour location and tumour stage, and that fascin immunoreactivity is an independent predictor of reduced OS and DFS in patients with advanced tumour stage. A growing body of literature reports that fascin is expressed in many types of transformed epithelial cell lines and in several solid neoplasms (Grothey et al, 2000;Hu et al, 2000;Goncharuk et al, 2002;Jawhari et al, 2003;Pelosi et al, 2003a, b;Hashimoto et al, 2004Hashimoto et al, , 2005aHashimoto et al, , 2006Tong et al, 2005;Xie et al, 2005;Yoder et al, 2005;Choi et al, 2006;Zhang et al, 2006) where it correlates with tumour stage (Hashimoto et al, 2004(Hashimoto et al, , 2005aYoder et al, 2005;Choi et al, 2006) and grade (Pelosi et al, 2003b;Hashimoto et al, 2004;Yoder et al, 2005), pT class (Hashimoto et al, 2004(Hashimoto et al, , 2005a, lymph node involvement (Hashimoto et al, 2004(Hashimoto et al, , 2005aChoi et al, 2006;Zhang et al, 2006), recurrence (Hashimoto et al, 2004), and both OS (Hashimoto et al, 2004(Hashimoto et al, , 2005a(Hashimoto et al, , 2006Yoder et al, 2005) and DFS (Pelosi et al, 2003b;Yoder et al, 2005). The close association we found between fascin immunoreactivity and tumour stage, tumour grade, the number and type of lymph node involvement, and distant metastasis indicates the major role of fascin in the progression of colonic adenocarcinoma.…”

“…Pelosi et al (2003b) also noted a differential distribution of fascin immunoreactivity in mucinous and nonmucinous bronchioloalveolar carcinomas of the lung and fascin transfection in colonic carcinoma cell lines increased the levels of neutral mucin (Jawhari et al, 2003). Although the clinical implications of colorectal mucinous carcinoma are still controversial, a consensus conference on colorectal carcinomas stated that mucinous and signet ring carcinomas, when evaluated jointly, have a poorer prognosis than intestinal-type adenocarcinomas (Compton et al, 2000).…”

Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade

“…Indeed, in a variety of human carcinomas, fascin expression is consistently associated with the clinical aggressiveness of the tumor. 18,19,21,23,24,26,33 Among the pancreatic neoplasms, IacobuzioDonahue et al 42 reported fascin upregulation for the first time in ductal adenocarcinoma using cDNA microarrays (13-fold overexpression of fascin transcripts in ductal adenocarcinoma compared with normal tissues). Immunohistochemical studies then confirmed fascin overexpression, not only in infiltrating ductal adenocarcinomas 28,30,31 but also in PanINs.…”

“…It is required for the formation of actin-based cell-surface protrusions that are essential for cellular migration and cellmatrix adhesion. [15][16][17] In normal epithelial cells, fascin expression is usually absent or very low, but it is significantly upregulated in transformed epithelial cells and several types of human carcinoma such as lung, 18,19 breast, [20][21][22][23] esophagus, 24,25 stomach, 26 colon, 27 pancreas, [28][29][30][31] biliary tract and ampulla, 31,32 ovary, 33 urinary bladder, 34 and skin. 35 Among the above neoplasms, fascin upregulation is most frequently observed in pancreatic infiltrating adenocarcinoma.…”