Fifteenth Issue of “Maimai” Pathology Weekly Reading Notes | Immunohistochemical Markers for Diagnosing Female Reproductive Tract Tumors (Part 1)

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6 2 月, 2026

On 6 2 月, 2026

Preface:

Malignant tumors can occur in almost all parts of the female reproductive tract, with cervical cancer being the most common, followed by others such as endometrial cancer and malignant ovarian tumors. With the deepening of research on traditional markers and the continuous discovery of new markers, immunohistochemistry plays an increasingly important role in the pathological diagnosis of female reproductive tract tumors. We have briefly summarized this content, which will be introduced in two parts, hoping to assist pathology colleagues in their diagnostic work.

Table 1. Commonly Used Immunohistochemical Markers for Vulvar and Vaginal Tumors

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Table2. Commonly Used Immunohistochemical Markers for Cervical Tumors

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Note:

Pax-2Generally expressed in benign hyperplastic endocervical glands;
In glandular componentsCK7positive;
In squamous componentsCK5/6、CK14positive.

Table 3. Commonly Used Immunohistochemical Markers for Uterine Body Tumors

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Note:

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

Table 4. Commonly Used Immunohistochemical Markers for Fallopian Tube and Uterine Ligament Tumors

Note:

Diffusely expressed in serous tubal intraepithelial carcinoma, but only a few scattered cells express it in normal fallopian tube mucosa.

Detailed Explanation of Some Markers

p16

Positive expression pattern: Nuclear/Cytoplasmic

Recommended positive control tissue: Cervical squamous cell carcinoma

p16is a tumor suppressor protein encoded by thep16^INK⁴^agene, functioning to inhibit cyclin-dependent kinases involved in cell cycle regulation and progression.p16Plays a role in the pathogenesis of many malignant lesions.p16expression is regulated by theRbgene, and theRbgene is influenced by theHPVoncogene in theE7gene, soHPV-related intraepithelial atypia and squamous cell carcinomas in multiple different sites (such as vulva, vagina, cervix, oropharynx) all exhibitp16overexpression.

In routine immunohistochemical detection,p16shows cytoplasmic and nuclear staining, and the staining intensity is related toHPVinfection and the degree of associated atypia. Meanwhile,p16is also highly expressed in uterine serous carcinoma and is a useful marker in the differential diagnosis of serous tubal intraepithelial carcinoma (serous tubal intraepithelial carcinoma，STIC).

Figure 1. Serous tubal intraepithelial carcinoma, HE-stained section shows significant atypia in the fallopian tube epithelium; on consecutive section immunohistochemical detection, these cellsp53show strong nuclear positivity, Ki-67proliferation index about 15%。

p16also helps differentiate atypical lipomatous tumor (well-differentiated liposarcoma) or other liposarcomas from benign lipogenic tumors, the former beingp16positive while the latter does not expressp16。

Pax-8

Pax-8is a transcription factor related to the development of fetal brain, eye, thyroid, kidney, upper urinary tract system, and Müllerian-derived organs; see the kidney and urinary tract tumor-related chapters for details.

HNF1β

Hepatocyte nuclear factor1β（Hepatocyte nuclear factor 1β，HNF1β) is a member of the hepatocyte nuclear factor family, regulating the growth and differentiation of hepatocytes and biliary system cells. The expression of different types of hepatocyte nuclear factors is not limited to the liver but can also be seen in other organs such as the pancreas, kidneys, prostate, and female reproductive system.

In practical work,HNF1β immunohistochemistry is used to differentiate various types of ovarian and endometrial cancers. Strong nuclear positive expression ofHNF1β is characteristic of endometrial and ovarian clear cell carcinomas, but it is generally negative in reactive lesions with clear cell features (such as clear cell metaplasia,Arias-Stellareaction). It should be noted that weak to moderate expression ofHNF1β can also be seen in other types of endometrial and ovarian cancers, such as endometrioid carcinoma and serous carcinoma. Additionally, other carcinomas of different origins may also show varying degrees ofHNF1β expression, such as colorectal, pancreatobiliary, prostate, and renal cell carcinomas.

PTEN

PTENis an enzyme widely expressed in mammalian cells, with functions related to apoptosis regulation. Mutations lead toPTENgene inactivation, resulting in inhibition of the apoptotic cascade and enhanced cell proliferation.PTENinactivating mutations are common in various human tumors, such as genitourinary tract, breast, lung cancers, malignant melanoma, and glioma.

PTENImmunohistochemical staining pattern (cytoplasmic staining) can easily detect the loss of this enzyme.PTENLoss of expression can be seen in30–50%of endometrial cancers, about25%of endometrial cases with atypical complex hyperplasia, indicating thatPTENloss of expression is not a specific marker for malignant transformation. Normal proliferative phase endometrium generally showsPTENstrong positive expression.PTENLoss of expression can also be seen in some ovarian endometrioid carcinomas (about20%), high-grade serous carcinomas, and clear cell carcinomas.GleasonIn higher-grade prostate cancers, some also showPTENloss of expression.PTENmutations are also seen in primary glioblastoma but are rare in secondary glioblastoma.

Steroid hormone receptors

ERandPRFor related details, refer to the breast tumor-related chapters. Both endometrial adenocarcinomas and serous carcinomas are sex hormone-dependent tumors, therefore they can expressER、PR. The uterine myometrium is also a target tissue for steroid hormones, so most uterine leiomyomas and leiomyosarcomas also expressERorPRor both. This can be used to differentiate uterine leiomyosarcoma from soft tissue leiomyosarcoma. Cervical squamous cell carcinomas and adenocarcinomas generally do not express these two receptors.

Mai Mai: “p16 is closely related to HPV infection-induced cervical cancer and can also assist in the differential diagnosis of serous carcinoma from other types of tumors. In the diagnosis of high-grade lesions, p16 expression is similar to histological diagnostic criteria, improving the accuracy of pathologists’ diagnoses and more accurately predicting the risk of high-grade lesions. Current research finds that Pax-8 is expressed in some subtypes of kidney, bladder, and thyroid tumors and in ovarian malignancies, but not in most epithelial tumors such as breast cancer, lung cancer, and malignant mesothelioma. Therefore, Pax-8 can serve as an effective marker for determining the primary site of tumors and for tumor differential diagnosis. Additionally, compared to uterine serous carcinoma, high-grade endometrioid carcinoma commonly shows PTEN loss of expression, thus it can be used for differential diagnosis between uterine serous carcinoma and endometrioid carcinoma. HNF1β is a good marker for ovarian clear cell carcinoma and can also serve as a marker for testicular germ cell tumors; combined use with Glypican-3 can help differentiate yolk sac tumor from other germ cell tumors.””

Antibody Name	Clone Number	Positive Control	Positive Location
^p16*	MX007	Cervical squamous carcinoma, tonsil	Nuclear/cytoplasmic
Pax-8*	MX062	Renal clear cell carcinoma, fallopian tube	Nuclear
^PTEN	6H2.1	Prostatic hyperplasia	Nuclear
HNF1β*	MX092	Renal clear cell carcinoma, appendix	Nuclear

*Marked as Maxim clone product

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