Table 3 Biomarkers for ovarian NENs

Immunohistochemistry

Ki-67

90%; mucinous cyst was border-line without stromal invasion.

Ki-67 antigen is overexpressed in malignant ovarian epithelial tumors. The higher expression signifies an aggressive tumor and a poorer prognosis.

[34, 38]

Chromogranin A

Positive in NEN cells.

It is a nonspecific marker and can be increased in non-neoplastic conditions such as inflammation. However, it is sensitive to rectal and ovarian NEN at higher levels (cut off 84–87 U/L).

[11, 39]

CD56

Positive in NEN cells.

An immunological marker for various types of ovarian tumors such as granulosa cell tumors, Sertoli-stromal cell tumors, large and small cell NECs, and ovarian NETs. Can differentiate neoplastic tumors from normal ovarian follicles.

[40]

Synaptophysin

Positive in NEN cells.

A common marker of neuroendocrine differentiation used in combination with other markers for diagnosing NENs. Positive results are associated with better or poorer prognosis in NENs at different sites.

[41]

TTF-1

Positive in NEN cells.

TTF-1 is used in the diagnosis of lung and thyroid carcinomas. May be positive rarely in serous and endometroid ovarian carcinoma.

[42]

• CEA

• CDX2

• PAX8

Positive in the adjacent Mucinous borderline tumor.

Negative in the NEN cells.

CEA is a nonspecific serum biomarker that is elevated in various malignancies, including mucinous ovarian cancer.

CDX2 and PAX8 are positive in epithelial tumors and differentiate epithelial from metastatic tumors.

- PAX8 positivity indicates primary NETs in the thyroid.

[43]

[44]

Calretinin inhibin

Negative in tumor cells.

Calretinin is positive in sex cord stromal tumors and is associated with a hyperandrogenic state.

Inhibin is a tumor marker for mucinous and granulosa cell tumors.

[45]

[46]

INSM1

Not done in our patient.

Equally or less sensitive but more specific for NETs than other markers such as synaptophysin and chromogranin.

[47, 48]