Thyroid transcription factor-1 (TTF-1), and cytokeratin 7 (CK7) and cytokeratin 20 (CK20) have recently been reported to be useful to distinguish between primary and metastatic lung adenocarcinoma. The aim of this study was to determine the usefulness of the staining patterns of pulmonary adenocarcinoma with antibodies to TTF-1, CK7, and CK20 in differentiating primary from metastatic pulmonary adenocarcinoma. Of the 66 lung adenocarcinoma specimens that were enrolled in our study, there were 40 primary lung adenocarcinomas, 12 metastatic adenocarcinomas from breast, 13 metastatic adenocarcinomas from colon, and 1 metastatic adenocarcinoma from stomach. The expression of TTF-1, CK7, and CK20 was assessed by immunohistochemistry. We found that 73% of primary lung adenocarcinomas expressed TTF-1, whereas all nonpulmonary adenocarcinomas lacked TTF-1 staining. CK7 expression was significantly more frequent in adenocarcinomas of pulmonary and breast origin than gastrointestinal (GI) origin (p < 0.001). In contrast, CK20 expression was significantly more prevalent in adenocarcinoma that originated in the GI tract than that of pulmonary or breast origin (p < 0.001). A combination of TTF-1+CK7+CK20- was highly significantly associated with primary adenocarcinoma of lung (vs GI tract, p < 0.001; vs breast, p < 0.001). A combination of TTF-1-CKCK20+ was highly significantly associated with adenocarcinoma of GI origin (vs lung, p < 0.001; vs breast, p < 0.001). Our study has confirmed that expression of CK7, CK20, and TTF-1 is a useful immunohistochemical marker for diagnosis of lung tumors and for differential diagnosis of primary pulmonary adenocarcinomas from extrapulmonary adenocarcinomas metastatic to the lung. Application of this panel of antibodies might be expected to increase the accuracy of diagnosis.

Our results indicate that HIF-1alpha is a key regulator of the angiogenic cascade. We show that HIF-1alpha is an independent prognostic factor for disease-free survival.

Our findings suggest that HIF-1alpha may play an important role in aggressive behavior and tumor angiogenesis in GIST. In addition, high expression of HIF-1alpha was significantly correlated with tumor recurrence/distant metastasis, so it may provide an ancillary prognostic factor for GIST.

Overexpression of Cyclooxygenase-2 in Urothelial Carcinoma: in conjunction with tumor-associated-macrophage infiltration, hypoxia-inducible factor-1a expression, and tumor angiogenesis. APMIS 2009; 117:176-84. This study examines whether the expression of cyclooxgenase-2 (COX-2) in urothelial carcinoma (UC) is associated with macrophage infiltration, hypoxia-inducible factor-1a (HIF-1a) expression and angiogenesis. We investigated the expression of COX-2 associated with HIF-1a and performed double immunohistochemical analysis of 216 UCs for COX-2 expression and the correlation with tumor-associated-macrophage (TAM) density and microvessel density (MVD) in situ. A high expression of COX-2 was positively correlated with tumor invasiveness, histologic grade and HIF-1a expression in UC (po0.0001, p = 0.003, po0.0001, respectively). Quantification of double staining of COX-2/CD34 and COX-2/CD68 showed that a higher MVD and TAM density was found in COX-2 high-expression than in COX-2 low-expression tumor fields (po0.0001). Adjacent to the principal of COX-2 expression areas, MVD value and TAM density were significantly increased in HIF-1a high-expression specimens compared with HIF-1a low-expression ones (po0.0001). Interestingly, our data revealed that high COX-2 expression (p = 0.002), high HIF-1a expression (po0.0001) and TAM density (po0.0001) were all associated with high MVD value. Our results suggest that COX-2 may produce a cooperative effect in promoting tumor progression and may be involved in the process of angiogenesis through increasing TAM infiltration or HIF-1a regulation by hypoxia.