Combination of MUC5ac and WT‐1 immunohistochemistry is useful in distinguishing pancreatic ductal carcinoma from ovarian serous carcinoma in effusion cytology

Abstract

Malignant ascites may be the first presentation of an unsuspected cancer. Pancreas and ovary are among the organs that are usually evaluated as a source of primary. The purpose of this study is to investigate a panel of immunohistochemical stains to help differentiate pancreatic from ovarian carcinoma. We evaluated the immunohistochemical staining of eight commercially available antibodies MUC1, MUC2, MUC5ac, Wilm's tumor susceptibility gene 1 (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous carcinomas were positive for WT-1 (100%), CK7 (93%), CK20 (43%), CA125 (100%), CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7 (78%), CK20 (22%), CA125 (89%), WT-1 (0%), and MUC 2 (0%). The combination of MUC5ac positivity/WT-1 negativity was seen in 100% of pancreatic carcinoma, whereas MUC5ac negativity/WT-1 positivity in 100% of ovarian serous carcinoma. It appears that the combination of MUC5ac and WT-1 stains is useful in distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid cytology.

Differential detection of cytoplasmic Wilms tumor 1 expression by immunohistochemistry, western blotting and mRNA quantification

“…There is little controversy regarding the observation that solid cancers of non-mesodermal origin rarely show nuclear immunostaining but frequently exhibit cytoplasmic immunostaining, while mesodermal tissues provide the nuclear immunostaining (8)(9)(10)(11)(12)(13)(14)(15)(16)(18)(19)(20)(21)(22)(23)(24)28). Differences of the conclusions about WT1 expression in non-mesodermal solid cancers stem largely from a discrepancy in interpretations of the cytoplasmic immunostaining.…”

“…Pathologists generally consider the cytoplasmic immunostaining for WT1 as non-specific reaction; they have described that WT1 is hardly expressed in nonmesodermal solid cancers such as colon cancer (0%) (11,15), pancreatic cancer (0%) (16), thyroid cancer (0%) (11), prostate cancer (0%) (11), lung cancer (0-20%) (8)(9)(10)(11)(12)(13)(14)(15) and breast cancer (0-7%) (11,13,15). The pathologists thus use WT1 to distinguish mesothelioma from lung cancers (8,(10)(11)(12)(13), or ovarian cancer cells from pancreatic cancer cells in malignant ascites (16). The present study scientifically supports the pathologists to judge the cytoplasmic immunostaining for WT1 as non-specific.…”

“…WT1, which contains four C-terminal zinc-finger motifs and an N-terminal DNA-binding domain, functions as a transcription factor in regulation of differentiation and development of mesodermally derived tissues such as kidney, mesothelium and gonad (3)(4)(5). WT1 has been reported to be strongly expressed in benign mesodermal tissues, as well as in malignancies of mesodermal origin such as leukemia (44-93%) (6,7), mesothelioma (72-100%) (8)(9)(10)(11)(12)(13)(14) and ovarian serous carcinomas (45-100%) (11,13,15,16). Therefore, WT1 mRNA is used as a clinical standard marker to diagnose minimal residual disease of leukemia (6) and immunohistochemical study for WT1 is helpful to distinguish mesodermally derived solid cancers such as mesothelioma and ovarian cancer from other solid cancers (8,(10)(11)(12)(13)15,16).…”

Diagnostic Usefulness of MUC1 and MUC4 for Distinguishing between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks

“…Because MUC1 and MUC4 are expressed mainly by the epithelial cells and are frequently overexpressed in carcinoma cells, it would be reasonable to anticipate its applicability in discriminating MAC from both benign and malignant mesothelial cells. However, studies on the expression of these mucins in body cavity fluids are limited [13,14,15,16,17,18]. Using immunocytochemistry, Han et al [18] analyzed expression of MUC1 in formalin-fixed paraffin-embedded cell blocks prepared from effusion specimens with evidence of metastatic carcinoma.…”

“…However, studies on the expression of these mucins in body cavity fluids are limited [13,14,15,16,17,18]. Using immunocytochemistry, Han et al [18] analyzed expression of MUC1 in formalin-fixed paraffin-embedded cell blocks prepared from effusion specimens with evidence of metastatic carcinoma. MUC1 immunoreactivity was detected in all cases of pancreatic (9 of 9; 100%) and ovarian carcinomas (14 of 14; 100%).…”