¹Department of Pathology and Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence: Dr G-Y Yang, MD, PhD, Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA. E-mail: g-yang@northwestern.edu

Received 3 January 2008; Revised 27 February 2008; Accepted 28 February 2008; Published online 6 June 2008.

Abstract

Clear cell carcinoma as a variant of ductal carcinoma of the pancreas is not well recognized. Hepatocyte nuclear factor-1 as a transcription factor has been identified as a specific biomarker of clear cell tumor of the female genital tract. The aim of this study was to systematically analyze clear cell carcinoma of the pancreas and its unique biomarker hepatocyte nuclear factor-1. A total of 84 pancreatic adenocarcinomas were analyzed pathologically and with an immunohistochemical approach with hepatocyte nuclear factor-1 antibody. The identified clear cell carcinomas were further studied by PAS, DPAS, and mucicarmine stains. Pathologic features and clinical follow-up were documented. Of them, 20 (24%) pancreatic adenocarcinomas were identified with clear cell features, including 12 clear cell carcinomas and 8 ductal adenocarcinomas with clear cell component (defined as less than 75% of tumor with clear cells). Cytologically, the clear cell carcinomas exhibited clear cytoplasm with centrally located, atypical nuclei. PAS, DPAS, and mucicarmine stains confirmed that the clear cytoplasm was not due to accumulation of glycogen or mucin. The results of immunostaining showed that hepatocyte nuclear factor-1 is overexpressed in all clear cell carcinomas and in the clear cell components of eight ductal carcinomas with clear cell features. In contrast, in usual ductal adenocarcinoma, hepatocyte nuclear factor-1 exhibited overall weak or focally moderate staining; only eight cases were strongly positive (15%) of which 38% were high grade and 63% were moderate grade. However, when included with the strong staining cases in mixed and clear cell carcinoma, this group regardless of morphology appeared to correlate with worse survival compared to the group with weak hepatocyte nuclear factor-1 staining across morphologies (P<0.01). Thus, clear cell carcinoma of the pancreas is not an uncommon variant of pancreatic ductal adenocarcinoma. Hepatocyte nuclear factor-1 is a useful marker to identify these clear cell carcinomas, and its overexpression may aid in stratifying survival rate.