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abstract
Immunohistochemistry in the Diagnosis of Mucinous Neoplasms Involving the Ovary: The Added Value of SATB2 and Biomarker Discovery Through Protein Expression Database Mining
Immunohistochemistry is frequently used to identify
ovarian mucinous neoplasms as primary or metastatic; however, there is
significant overlap in expression patterns. We compared traditional
markers (CK7, CK20, CDX2, PAX8, estrogen receptor, β-catenin, MUC1,
MUC2, and MUC5AC) to 2 novel proteins identified through mining of the
Human Protein Atlas expression database: SATB2 and POF1B. The study
cohort included 49 primary gastrointestinal (GI) mucinous
adenocarcinomas (19 colorectal, 15 gastric, 15 pancreatobiliary), 60
primary ovarian mucinous neoplasms (19 cystadenomas, 21 borderline
tumors, 20 adenocarcinomas), and 19 metastatic carcinomas to the ovary
(14 lower and 5 upper GI primaries). Immunohistochemistry was performed
on tissue microarrays, scored and interpreted as negative (absent or
focal/weak) or positive. Metastatic tumors were frequently unilateral
(42.8% of tumors from lower and 40% of tumors from upper tract) and ≥10
cm (85.7% of tumors from lower and 80% of tumors from upper tract). CK7
was positive in 88.5% upper GI and 88.3% primary ovarian compared with
24.3% lower GI neoplasms. CK20 and CDX2 were positive in 84.8% and 100%
of lower GI tumors, respectively; however, expression was also common in
upper GI (CK20 42.8%, CDX2 50%) and primary ovarian neoplasms (CK20
65.7%, CDX2 38.3%). Conversely, SATB2 was more specific for lower GI
origin, being positive in 78.8% lower GI but only 11.5% upper GI and
1.7% primary ovarian neoplasms. PAX8 expression was common in primary
ovarian neoplasms (75% of all neoplasms, 65% of carcinomas); only 1
(1.5%) GI tumor was positive. MUC2 and β-catenin were frequently
positive in lower GI tumors (96.9% and 51.5%, respectively). Estrogen
receptor expression was only seen in primary ovarian neoplasms (13.3%).
Nuclear premature ovarian failure 1B (POF1B) expression was seen in
malignant tumors regardless of their origin. A panel including CK7,
SATB2, and PAX8 separated primary from secondary GI neoplasms with up to
77.1% sensitivity and 99% specificity, outperforming tumor laterality
and size. Second-line markers such as CDX2, MUC2, estrogen receptor,
MUC1, and β-catenin increased the sensitivity of immunohistochemistry in
excluding lower GI origin. Biomarker search using proteomic databases
has a value in diagnostic pathology, as shown with SATB2; however, as
seen with POF1B, expression profiles in these databases are not always
reproduced in larger cohorts.
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