SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type

Abstract

The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric adenocarcinomas showed any SATB2 staining. In a subset of tumors for which CK7, CK20, and CDX2 were available, SATB2 was never positive in any tumor of any origin that was CK7+CK20-CDX2-. Among tumors that coexpressed all 3 markers (CK7+CK20+CDX2+), 6/7 SATB2 tumors were of colorectal or appendiceal origin, and 1/7 was a primary ovarian borderline tumor. We conclude that ovarian tumors with mucinous or endometrioid features that express SATB2 are unlikely to be of primary ovarian origin unless there is a component of mature teratoma in the ovary; instead, attention should be directed to a colorectal or appendiceal origin. SATB2 may be of particular value in ovarian mucinous tumors that are positive for all 3 markers (CK7+CK20+CDX2+), as SATB2 staining strongly implicates a colorectal or appendiceal origin.

SATB2 in neuroendocrine neoplasms: strong expression is restricted to well‐differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas

“…In their discussion, they shared an unpublished observation that SATB2 expression is seen in a ‘majority of NETs of the colon, rectum, and appendix but rarely in NETs from the stomach, duodenum, small intestine, pancreas, and lung’. Moh et al ., in a study focused on the distinction of lower GI tract adenocarcinomas metastatic to the ovary from mucinous ovarian or endometrioid primaries, reported SATB2 negativity in one ‘small intestinal carcinoid’ metastatic to the ovary . Finally, in a study focused on identifying sensitive and specific colon cancer diagnostic makers, Li et al .…”

Relatively Poor Survival of Mucinous Ovarian Carcinoma in Advanced Stage: A Systematic Review and Meta-analysis

“…38,39 Markers recently introduced in gynecological pathology, such as PAX-8 and SATB2, might further facilitate diagnosing correctly and reducing numbers of falsepositive cases of primary MOCs. 40,41 Retrospective studies suggest that the unfavorable prognosis of patients with advanced-stage MOC is caused by a resistance to currently used chemotherapy regimens. 4,7,9,42 Several protocol changes have been implemented in the past decades, such as the introduction of cisplatin in the early 1970s and of paclitaxel in the early 1990s.…”

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

“…SATB2 expression is virtually absent in primary ovarian mucinous tumors ( Figure 2, A and B) unless a component of mature teratoma is present. [64][65][66] In contrast, SATB2 is frequently expressed in low-grade appendiceal mucinous neoplasms ( Figure 2, C and D). SATB2 also appears to be a reliable marker that can be used to distinguish metastatic adenocarcinoma of appendiceal origin from primary ovarian adenocarcinoma.…”

“…SATB2 also appears to be a reliable marker that can be used to distinguish metastatic adenocarcinoma of appendiceal origin from primary ovarian adenocarcinoma. In the study by Moh et al, 64 for example, SATB2 expression was observed in 8 of 10 low-grade appendiceal mucinous neoplasms and 4 of 4 high-grade appendiceal adenocarcinomas that metastasized to the ovaries. In primary ovarian tumors, SATB2 was detected in 0 of 22 mucinous cystadenomas, 4 of 12 mucinous cystadenomas with mature teratomatous components (33%), 1 of 60 mucinous borderline tumors (1.6%), 0 …”