Maimai’s Pathology Weekly Reading Notes Issue 16 | Immunohistochemical Markers for Diagnosing Female Genital Tract Tumors (Part 2)

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6 2 月, 2026

On 6 2 月, 2026

Preface:

In the previous article, we mainly introducedFemale reproductive tract organsthe commonly used immunohistochemical markers for tumors of the external genitalia and vagina, cervix and uterine body, as well as fallopian tubes and uterine ligaments. In this issue, we will systematically review and explain theCommonly used immunohistochemical markersof various ovarian tumors, hoping that through such introductions, we can provide some reference for pathology colleagues in selecting corresponding tumor immunohistochemical markers.

Table 1. Commonly used immunohistochemical markers for ovarian epithelial tumors

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Note:

High expression is characteristic in high-grade serous carcinoma, while low expression or negative in low-grade carcinoma;
CDX-2 and CK20 are positive in mucinous adenocarcinoma and intestinal-type adenoma;
Generally negative in adenoma and borderline tumors;
Basal epithelial cells express CK5/6/14.

Table 2. Commonly used immunohistochemical markers for ovarian sex cord-stromal tumors

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Table 3. Commonly used immunohistochemical markers for ovarian germ cell tumors

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Table 4. Commonly used immunohistochemical markers for other ovarian tumors

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Note:

In mucinous endometrioid adenocarcinoma,CDX-2can be positive;
p16andp53positivity is generally only seen in leiomyosarcoma;
In placental site nodule and exaggerated placental site,Ki-67proliferation index<1%, in choriocarcinomaKi-67proliferation index>50%。

Detailed explanation of some markers

WT-1

Positive expression pattern: nuclear

Recommended positive control tissue: Wilms tumor, mesothelioma, etc.

WT-1 is a transcription regulator that plays an important role in the regulation of growth factors and the development of tissues from the inner layer of intermediate mesoderm (specifically the reproductive system, mesothelial cells, spleen). Mutations in the DNA-binding domain of the WT-1 gene can lead to the development of Wilms tumor.

In routine immunohistochemistry, WT-1 has two different staining patterns: first, true nuclear staining, which is characteristic of many tumors, such as serous carcinomas of ovarian, fallopian tube, and peritoneal origin, and mesothelioma. Second, cytoplasmic staining, which can be seen in endometrial and vascular tumors, as well as some tumor types such as lung adenocarcinoma. Cytoplasmic staining appears to be due to cross-reactivity of the antibody with antigens unrelated to WT-1. Endometrioid carcinoma, clear cell carcinoma, transitional cell carcinoma, and mucinous carcinoma generally do not express WT-1 or show only focal weak positivity. WT-1 also helps differentiate WT-1 positive tumors from many morphologically similar WT-1 negative tumors, such as distinguishing Wilms tumor from PNET group tumors.

WT-1 has a high positive rate in epithelioid mesothelioma, which helps differentiate peritoneal carcinomatosis of ovarian origin from primary peritoneal mesothelioma. Other immunohistochemical markers such as Pax-8, Ber-EP4, and calretinin are also helpful in this regard.

Figure 1. Ovarian serous carcinoma, immunohistochemistry shows strong nuclear positivity for WT-1.

CA125

Positive expression pattern: cell membrane (luminal)

Recommended positive control tissue: ovarian serous carcinoma

CA125 is a high molecular weight glycoprotein, normally expressed in glandular epithelium of various organs, and highly expressed in ovarian serous carcinoma and clear cell carcinoma. Serum CA125 levels also help monitor the progression of ovarian cancer.

Figure 2. Ovarian serous carcinoma, immunohistochemistry shows cell membrane staining for CA125.

However, CA125 is expressed in many different epithelial and non-epithelial malignant tumors and is not specific for ovarian cancer. Mesothelioma can also express CA125.

FOXL2

Positive expression pattern: nuclear

Recommended positive control tissue:Ovarian tissue (granulosa cells)

This is a transcription factor related to the development of the ovary and female reproductive tract. High expression of FOXL2 is associated with testicular and ovarian sex cord-stromal tumors, such as adult and juvenile granulosa cell tumors, thecoma/fibroma, Sertoli/Leydig cell tumors, and sclerosing stromal tumors. Some pituitary adenomas also express FOXL2, such as gonadotroph adenomas and most null cell adenomas. Ovarian surface epithelial tumors and germ cell tumors do not express FOXL2.

Pax-8

As mentioned earlier, Pax-8 is a transcription factor highly expressed in Müllerian-derived glandular epithelium, renal tubules, and the upper urinary tract system. Therefore, it is highly expressed in Müllerian-derived tumors of the uterus, endocervix, and ovary, specifically such as serous carcinoma, clear cell carcinoma, endometrioid carcinoma, etc.; it will be discussed in detail in the chapter on renal cell tumors.

Maimai: “CA 125 is a major marker for epithelial ovarian cancer, especially serous carcinoma, and has reference value in the differential diagnosis of serous carcinoma and mucinous carcinoma. Pax-8 is highly expressed in ovarian serous carcinoma but almost not expressed in ovarian mucinous carcinoma. Therefore, the positive expression of both has its specific reference significance. Besides the important roles mentioned above, the WT-1 marker can also be used in the differential diagnosis of some small round cell tumors, etc.””

Antibody Name	Clone Number	Positive Control	Positive Location
^{CA 125*}	MX055	Ovarian serous carcinoma, fallopian tube	Cytoplasm/Cell membrane
Pax-8*	MX062	Renal clear cell carcinoma, fallopian tube	Nucleus
^WT-1*	MX012	Kidney tissue, Wilms tumor	Nucleus

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