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Expression of SMAD4 is Retained in Most Gynecologic Tumors with Mucinous Differentiation
Abstract:
SMAD4 is a tumor suppressor gene that plays a role in cancer initiation and progression. A few studies have explored the value of immunohistochemistry for SMAD4 in gynecologic neoplasms, mainly in the ovary. However, literature is sparse when it comes to other sites such as endometrium and cervix, as well as in benign and borderline ovarian mucinous neoplasms. The aim of this study was to assess the expression of SMAD4 in various gynecologic tumors. We selected primary gynecologic tumors comprising a spectrum of neoplasms showing mucinous differentiation. Few cases of metastatic tumors were also included. A total of 103 cases were retrieved, including tumors of ovarian origin (13 mucinous adenocarcinomas, 9 mucinous borderline tumors, 19 mucinous cystadenomas, and 3 mucinous tumors arising from teratomas), 36 of endometrial origin (23 endometrioid adenocarcinomas with mucinous differentiation and 13 mucinous adenocarcinomas), 17 cases of cervical carcinoma (16 of usual type and 1 of gastric type), and 6 metastatic adenocarcinomas to ovary. SMAD4 immunohistochemistry was retained in most primary tumors, except in 3 endocervical adenocarcinomas (2 usual-type, 1 gastric-type) and in one mucinous carcinoma arising from an ovarian teratoma. Of the 6 metastatic cases, 4 showed SMAD4 loss. In summary, retained expression of SMAD4 was seen in 95.8% of primary gynecologic neoplasms. These results can be of utility when dealing with mucinous lesions for which metastatic origin is suspected. Loss of SMAD4 expression virtually excludes primary tumors of endometrial or ovarian origin, but is of less utility when evaluating carcinomas involving the cervix.
Insights
SMAD4 immunohistochemistry is retained in most primary gynecologic tumors, aiding in distinguishing primary from metastatic mucinous lesions. Loss of SMAD4 expression is useful for excluding primary endometrial or ovarian tumors.
Area of Science:
- Gynecologic Oncology
- Molecular Pathology
- Tumor Suppressor Genes
Background:
- SMAD4 is a critical tumor suppressor gene involved in cancer development.
- Limited research exists on SMAD4 immunohistochemistry in endometrial, cervical, and benign/borderline ovarian mucinous neoplasms.
- Understanding SMAD4 expression aids in gynecologic tumor diagnosis.
Purpose of the Study:
- To evaluate SMAD4 expression across a spectrum of primary and metastatic gynecologic mucinous tumors.
- To assess the diagnostic utility of SMAD4 immunohistochemistry in differentiating primary gynecologic neoplasms.
Main Methods:
- Retrospective analysis of 103 gynecologic tumors with mucinous differentiation.
- Inclusion of primary ovarian, endometrial, and cervical tumors, plus metastatic ovarian adenocarcinomas.
- SMAD4 immunohistochemistry performed on all retrieved cases.
Main Results:
- SMAD4 expression was retained in 95.8% of primary gynecologic neoplasms.
- Loss of SMAD4 was observed in 3 endocervical adenocarcinomas and 1 ovarian teratoma-derived mucinous carcinoma.
- SMAD4 loss was noted in 4 out of 6 metastatic adenocarcinomas to the ovary.
Conclusions:
- Retained SMAD4 expression is characteristic of most primary gynecologic mucinous neoplasms.
- SMAD4 loss is valuable for suspecting metastatic origin in mucinous lesions.
- SMAD4 loss helps exclude primary endometrial and ovarian tumors but is less definitive for cervical carcinomas.
