3855

KRT7

keratin 7, type II;KRT7;keratin 7, type II

CK-7|cytokeratin 7|cytokeratin-7|keratin, 55K type II cytoskeletal|keratin, simple epithelial type I, K7|keratin, type II cytoskeletal 7|keratin-7|sarcolectin|type II mesothelial keratin K7|type-II keratin Kb7

12q13.13

protein-coding

There are limited data regarding CDX2 expression in rectal carcinoma. The CK20/CK7 immunoprofile of colorectal adenocarcinoma has been described in studies, which have mostly lumped colonic and rectal tumors together. In this study, we investigated the diagnostic utility of immunohistochemical stains for CK7, CK20, and CDX2 in a series of rectal adenocarcinoma. Fifty-five specimens of rectal adenocarcinomas were retrieved and immunostained for CK7 (Dako-M7018), CK20 (NovoCastra NCL-L-CK20), and CDX2 (NovoCastra NCL-CDX2). Thirty cases of pancreatic adenocarcinoma and 15 cholangiocarcinomas were also studied as a comparison group. CK7 was expressed in 12/55 (22%) and CK20 in 48/55 (87%) cases of rectal adenocarcinoma. The CK7-/CK20+ immunophenotype was identified in 36/55 (65%), CK7+/CK20+ in 12/55 (22%), and CK7-/CK20- in 7/55 (13%) rectal adenocarcinoma. CDX2 showed moderate-strong positivity in all cases and was not related to tumor differentiation. Benign rectal mucosa was available in 37 cases and showed the following results: CK7-/CK20+ in 25/37 (67%), CK7+/CK20+ in 8/37 (22%) and CK7-/CK20- in 4/37 (11%) cases. In pancreatic adenocarcinomas and cholangiocarcinomas, 29/45 (64%) were CK7+/CK20+ and 16/45 (36%) were CK7+/CK20-. CDX2 was positive in only 3/45 (7%) of these cases; all were pancreatic adenocarcinomas. In conclusion, CK7 can be expressed in rectal adenocarcinoma, and should not be used as the sole basis for excluding a rectal primary. CDX2 is a sensitive marker for rectal origin of adenocarcinoma. It can be helpful in cases with metastatic rectal carcinoma, especially those with CK7+/CK20+ or CK20-/CK7- immunophenotype. In this study, CDX2 expression was not influenced by the grade (differentiation) of rectal adenocarcinoma.

We report the case of a 51-year-old woman with pulmonary adenocarcinoma with enteric differentiation (PAED) that is indistinguishable from metastatic colorectal carcinoma by immunohistochemistry as well as histology. A chest computed tomography scan revealed a 1cm nodule in the right upper lobe and a 3cm mass in the left lower lobe. Initial examination showed no evidence of any other tumor. She underwent partial resection of the right upper lobe and left lower lobectomy. Histopathological examination revealed that both tumors were composed of medium to large complex glands with central necrosis. The tumor cells were cuboidal to tall columnar with eosinophilc cytoplasm, oval nuclei, and brush-border. Immunohistochemical study yielded the following results: tumor cells were diffusely positive for cytokeratin (CK) 20 and CDX-2, and negative for CK7, thyroid transcription factor-1, and Napsin A. MUC2 was partially observed, while MUC5AC was not detected. These findings were strongly indicative of metastatic colorectal carcinoma. However, no primary colorectal cancer was detected in any clinical examination, including fluorine 18-labeled fluorodeoxyglucose-positron emission tomography scan and video capsule endoscopy, and she has not presented with any characteristic symptoms at any follow-up to date, approximately 4 years after operation. From all features, the final diagnosis was primary PAED, suggestive of multifocal primary lung cancer. So far, only 1 case of CK7-negative PAED has been reported. This is the second case of primary PAED resembling metastatic colorectal cancer morphologically and immunohistologically.

Prognosis of cancers with lymph node metastasis is known to be very poor; however, it is still controversial whether metastatic potential can be evaluated by expression profiles of primary tumors. Therefore, to address this issue, we compared gene expression profiles of 24 esophageal squamous cell carcinomas (ESCCs) with extensive lymph node metastasis and 11 ESCCs with no metastatic lymph node. However, there was no gene cluster distinguishing these two groups, suggesting that lymph node metastasis-associated genes are varied depending on cases or subgroups. Therefore, we applied a recently developed filtering method (S2N') to identify such genes, and successfully extracted 209 genes associated with node status. Among them, over-expression of CALB1, KRT7/CK7, MUC1 and CEA/CEACAM5 in poor prognostic cases with metastatic lymph nodes was confirmed in two sets of ESCCs by RT-PCR. Each often seemed to have glandular cell type-characteristics in both the gene expression and morphology. It was also revealed that FOXA1 siRNA treatment of esophageal cancer cells reduced the mRNA level of both KRT7 and a stabilizer of epithelial-mesenchymal transition (EMT) regulator LOXL2, and that both FOXA1 and LOXL2 siRNAs reduced invasion and migration of ESCC cells. In 15 KRT7-expressing ESCCs with metastatic lymph nodes, 60% expressed FOXA1 and 33% expressed both FOXA1 and LOXL2. These results suggest that FOXA1 induces not only KRT7 but also LOXL2 in a subset of poor prognostic ESCCs with metastatic lymph nodes, and it is also plausible, that other FOXA1 downstream genes could be therapeutic targets of poor prognostic ESCCs.

Dynamin 2 is known as a protein involved in cell migration and endocytosis. We aimed to investigate the association between dynamin 2 expressions and tumor progression in early cervical carcinoma (IB1-IIA). Dynamin 2 expression was evaluated at protein level in thirty seven paraffin-embedded, formalin-fixed tissues including four normal cervix tissues and compared with pathologic risk factors for recurrence after surgery in thirty three patients with squamous cell carcinoma of the cervix. The expression of dynamin 2 was not different according to clinical stage and lympho-vascular space invasion. However, there were inverse correlations between dynamin 2 expression and the depth of invasion in cervix (p = 0.003) and lymph node (LN) metastasis (p = 0.001). To evaluate the mechanism of dynamin 2 in tumor invasion and metastasis, we performed an in vitro experiment with dynamin 2 siRNA using several cervical carcinoma cell lines such as HeLa, MS751 and SiHa cells. We found the inhibition of dynamin 2 using specific siRNA enhanced the expression of matrix metalloproteinase-2. These results suggested that dynamin 2 might be involved in preventing tumor invasion and LN metastasis, possibly in relation with extracellular matrix degradation, and may be a prognostic marker for these risk factors in early squamous cell carcinoma of the cervix.