Diagnostic value of the combined use of SATB2 and CDX2 in mucinous carcinoma of colorectal origin

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Abstract

Background

Metastatic mucinous adenocarcinoma from an unknown primary site is a frequent clinical dilemma. The ability to confirm or exclude a diagnosis of carcinoma of colorectal origin by immunohistochemistry has been limited by the lack of a reliable positive marker for colorectal differentiation. Caudal type homeobox 2 (CDX2) has been reported to be expressed in intestinal adenocarcinomas; yet, it is also expressed in other tumors such as those of the pancreas, bile ducts, bladder, endometrium, and ovary. Special AT-rich sequence-binding protein 2 (SATB2) has been recently linked to colorectal cancer. The diagnostic role of SATB2 in mucinous carcinoma of colorectal origin has not been previously elaborated.

Aim

The aim of this study was to investigate the diagnostic value of SATB2 in differentiating mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins as compared with that of CDX2.

Materials and methods

A comparative immunohistochemical study of SATB2 and CDX2 expression was performed in 42 cases of primary mucinous carcinomas (colorectal=10, breast=14, cervix=10, stomach=8) and 22 cases of metastatic mucinous colorectal carcinoma. The predictive capacity of SATB2 and CDX2 expression for diagnosing the mucinous carcinoma of colorectal origin was determined individually and in combination using sensitivity, specificity, and positive and negative predictive value calculations.

Results

SATB2 demonstrated positive immunoreactivity in all cases of primary colorectal carcinoma and 81.8% of metastatic colorectal carcinomas in addition to 57.1% of breast, 40% of cervical, and 25% of gastric tumors. CDX2 was positively expressed in 60% of primary colorectal carcinomas and 72.7% of metasty tatic colorectal carcinomas, but it was negative in all noncolonic primary mucinous carcinomas. The SATB2 expression showed a sensitivity of 100% and a specificity of 56.2% in identifying colorectal origin of mucinous carcinomas, compared with 60 and 100% for CDX2 expression, respectively. The combined use of both SATB2 and CDX2 raised both the sensitivity and the negative predictive values to 100% if any of the two markers showed positivity as compared with the isolated use of CDX2.

Conclusion

SATB2 is a more sensitive yet less specific marker for diagnosis of mucinous carcinoma of colorectal origin as compared with CDX2. SATB2 in combination with CDX2 increases the accuracy of distinguishing mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins; therefore, SATB2 is considered a useful marker in this respect.

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