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The utility of SMAD4 as a diagnostic immunohistochemical marker for pancreatic adenocarcinoma, and its expression in other solid tumors
Author(s) -
Ali Sarfraz,
Cohen Cynthia,
Little James V.,
Sequeira Judy H.,
Mosunjac Marina B.,
Siddiqui Momin T.
Publication year - 2007
Publication title -
diagnostic cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.417
H-Index - 65
eISSN - 1097-0339
pISSN - 8755-1039
DOI - 10.1002/dc.20715
Subject(s) - adenocarcinoma , pathology , immunohistochemistry , medicine , pancreas , tissue microarray , melanoma , cancer , cancer research
Pancreatic adenocarcinoma is a genetic disease showing somatic mutations of multiple genes, including SMAD4. SMAD4 is a tumor suppressor gene that is inactivated in a sub‐set of pancreatic adenocarcinoma, either by the intragenic mutation of one allele in combination with the loss of the other allele or by homozygous deletion of both alleles. This study examines SMAD4 expression in fine‐needle aspiration cell blocks from patients with pancreatic adenocarcinoma, as well as a variety of human cancers, in order to assess its viability as a tumor marker. A total of 100 patients with pancreatic adenocarcinoma, with diagnostic material from fine‐needle aspiration cell blocks were selected for this study. In addition cancers from different sites were examined in multitumor tissue microarrays, which included two tissue cores from neoplastic surgical resection specimens. Cancers studied included endometrium ( n = 100), colon ( n = 100), ovary ( n = 100), lung ( n = 100), breast ( n = 100), and malignant melanoma (n = 100). The sections were immunostained with SMAD4 using pressure cooker antigen retrieval labeled polymer horseradish peroxidase (DAKO), and the DAKO autostainer. Immunohistochemical expression was scored as negative, 1+, 2+, 3+. Only 2+ and 3+ staining was considered as positive staining. SMAD4 staining was nuclear and the results for tumor cell positivity for primary sites studied are as follows: Pancreas (80/100; 80%), endometrium (0/100; 0%), colon (0/100; 0%), ovary (3/100; 3%), lung (0/100; 0%), breast (2/100; 2%), and malignant melanoma (4/100; 4%). This study suggests that SMAD4 is an important marker for confirming a diagnosis of pancreatic adenocarcinoma as a primary tumor, as well as when it presents as a metastatic tumor on small fine‐needle aspirate samples. Diagn. Cytopathol. 2007;35:644–648. © 2007 Wiley‐Liss, Inc.