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Year : 2018  |  Volume : 2  |  Issue : 1  |  Page : 1-2

Role of immunohistochemistry in gynecological malignancies

Department of Pathology, SCB Medical College, Cuttack, Odisha, India

Date of Web Publication23-Mar-2018

Correspondence Address:
Dr. Asaranti Kar
Department of Pathology, SCB Medical College, Cuttack, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/oji.oji_8_18

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How to cite this article:
Kar A. Role of immunohistochemistry in gynecological malignancies. Oncol J India 2018;2:1-2

How to cite this URL:
Kar A. Role of immunohistochemistry in gynecological malignancies. Oncol J India [serial online] 2018 [cited 2023 Jun 2];2:1-2. Available from: https://www.ojionline.org/text.asp?2018/2/1/1/228328

Surgical pathology has the definitive role in tumor diagnosis. In spite of the high index of clinical suspicion, the diagnosis of cancer cannot be conclusively established without tissue diagnosis. The surgical pathologists provide an accurate, specific, and comprehensive diagnosis to develop an optimal plan of treatment and estimate prognosis. Details of the type and origin of the tumor, its differentiation, level of invasion, the numbers of lymph nodes with or without metastasis, the presence or absence of hormone receptors, the activity of specific enzymes, ploidy, frequency of mitosis, and percentage of cells in the S-phase are relevant in the pathologic assessment of neoplasia. Methods for obtaining surgical specimens are needle biopsies, incisional and excisional biopsies. Hematoxylin and eosin (H and E) staining is the gold standard of pathologic diagnosis and will probably remain the mainstay of morphologic interpretation for the next few decades.[1] However, many new techniques are routinely available now that can aid in the differentiation of lesions with overlapping histologic features. One such technique is the use of immunohistochemistry (IHC), which allows for the detection of protein expression enabling differentiation of the cells comprising the sample. Gynecological pathology also needs utilization of IHC to supplement the use of H and E-stained sections for arriving at a diagnosis, planning for further treatment, and to predict prognosis. All gynecologists would benefit from a more thorough understanding of the clinical–pathologic applications of IHC in clarifying and confirming pathologic diagnosis on which prognosis and further management are determined.[2]

Use of IHC is based on the principle of detection of a particular protein or antigen on or within a cell with the commercially available antibody. This antibody-antigen complex is then magnified and tagged with a stain that is visible under the light microscope. IHC can help in definite diagnosis, monitoring therapeutic response, prognosis, histogenesis and detecting unknown primaries.

Uterus: In uterus, IHC plays an important role in differentiation of atypical hyperplasia versus cyclic endometrium versus endometrioid carcinoma by the use of phosphatase and tensin homolog (PTEN). PTEN is a tumor suppressor gene which plays important role in the development and progression of endometrioid carcinoma. There occurs functional loss of this gene product which can be detected by negative staining in IHC. Cyclic endometrium reveals a diffuse positive staining pattern with PTEN IHC whereas endometrial hyperplasia gives intermediate and endometrioid carcinoma negative staining helping in differentiation of these three closely mimicking entities. Distinguishing usual and endometrioid type endocervical adenocarcinomas from endometrial endometrioid adenocarcinoma (EEA) are of clinical and prognostic importance. Endocervical adenocarcinoma is almost always associated with high-risk HPV infection, and therefore, they exhibit strong and diffuse nuclear staining with p16 immunostain as a result of inactivation of Rb by HPV E7 protein whereas EEA is negative or only focally and weakly positive for p16 in the glandular component.[3] Immunomarkers like carcinoembryonic antigen is positive, and vimentin and hormone receptors (estrogen receptor and/or progesterone receptor) are negative in most of the endocervical adenocarcinoma, whereas, reverse is found in EEA. Distinction between the different histological subtypes of endometrial adenocarcinoma (EAC) has major clinical and prognostic implications which need help of IHC in addition to histopathology. Among type II endometrial carcinomas, serous carcinoma shows abnormal p53 protein expression pattern by IHC 70 in 90% of the cases due to p53 mutations. Clear cell adenocarcinoma and EEA reveal weak and focal p53 staining. P16 staining is weak and patchy to negative in endometrioid and clear cell carcinoma but positive in serous EAC. IHC is often necessary to distinguish between endometrial stromal and smooth muscle differentiation in uterine mesenchymal neoplasms. Endometrial stromal tumors exhibit diffuse, strong staining with CD10. However, smooth muscle tumors express smooth muscle actin (SMA), desmin, and h-caldesmon. However, there is considerable overlap in the immunohistochemical profile. On the other hand, high-grade stromal sarcomas are negative for all these immunomarkers except Cyclin D1.

Ovary and  Fallopian tube More Detailss: Pelvic or nonuterine high-grade serous carcinomas including ovarian, tubal, and primary peritoneal serous carcinomas have high mortality, rapid progression, and poor prognosis. The cause is lack of understanding of pathogenesis and a proper screening method. Over last decade, research has pointed to fallopian tube as the precursor site for these malignancies. Demonstration and documentation of serous tubal intraepithelial lesions and serous tubal intraepithelial carcinoma require immunostaining with p53 and Ki67 as there is variation in histomorphologic interpretation of these lesions among pathologists.[4] The differential diagnosis between the histological subtypes of primary ovarian carcinoma can often be resolved by thorough assessment of H and E microscopic features. However, significant morphologic overlap exists, especially between high-grade ovarian carcinomas (i.e., high-grade serous, clear cell, and endometrioid adenocarcinomas), requiring additional immunohistochemical workup. P53 mutations are present in nearly all high-grade serous carcinomas of the ovary. Nuclear immunoreactivity for Wilms tumor 1 (WT-1) is also characteristic of ovarian serous carcinoma, both low- and high-grade subtypes, whereas clear cell and endometrioid carcinomas are WT-1 negatives. Rest of the markers are similar to their uterine counterparts. Another important application of IHC is in the distinction between primary and metastatic mucinous carcinomas. Primary mucinous carcinomas are CK7 positive and variably positive (around 50% cases) for paired box gene 8 (PAX8), but more than 90% of nonmucinous ovarian carcinomas express PAX8 positivity.[5] Alpha-inhibin and calretinin are positive in sex cord tumors but negative to variably positive in ovarian carcinoma, respectively.

  Gestational Trophoblastic Disease Top

P57, a cyclin-dependent kinase inhibitor protein encoded by the CDKN1C gene on chromosome 11, is suitable for differentiating between CHMs (negative staining) and its mimics that contain maternal genetic materials such as PHMs, hydropic nonmolar abortions, and trisomies which show normal p57 protein expression.[6] The use of IHC can help in distinguishing gestational trophoblastic disease (GTD) from GTD mimics such as epithelial and mesenchymal tumors and also helps in differentiating among different entities of GTD. Various recent studies have selected and segregated three most important markers such as Cyclin E, p63, and Ki67 which are classical and can help out in differentiation and also correlate well with the FIGO prognostic scoring system. Expression of Cyclin E and Ki67 are low in partial moles, but p63 is moderate. In hydropic abortus, all the markers are zero differentiating it from molar gestation. In complete moles, expression of p63 is low, but Cyclin E and Ki67 are very high, thus differentiating it from normal placenta, hydropic abortus, and partial moles. Lesions of intermediate trophoblasts such as exaggerated placental site (EPS) and placental trophoblastic tumor (PSTT) express high score of Cyclin E, but Ki67 is zero in EPS and high in PSTT. Epithelioid trophoblastic tumor (ETT) can be differentiated from PSTT by p63 which is high in ETT. Choriocarcinoma expresses very high Cyclin E and Ki67 but low p63. Hence, by using these three immunomarkers, one can comfortably distinguish different entities of GTD.

  Lower Female Genital Tract Top

Precursor lesions (intraepithelial neoplasia) of lower female genital tract such as the cervix, vagina, and vulva have typical histomorphologic features. However, there are several mimics and lot of intra- and inter-observer variation between the lesions. IHC for overexpression of p16 can help in definite diagnosis of low-grade and high-grade squamous intraepithelial lesions (SIL). At the same time, p16 may be negative between 8% and 28% cases of SILs. Therefore, it should be evaluated along with morphologic features and Ki67 IHC. Recent studies suggest that a combined immunohistochemical panel consisting of ProExC and p16 can still improve the specificity and positive predictive value for CIN2/3, sensitivity might decrease.[7],[8]

IHC is a very important diagnostic tool in the evaluation of surgical pathology specimens. However, it cannot replace conventional histopathology, is expensive, and has many technical problems. Therefore, it should always be used in association with clinical, radiological, and histomorphological findings.

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There are no conflicts of interest.

  References Top

Shutter J, Atkins KA, Ghartey K, Herzog TJ. Clinical applications of immunohistochemistry in gynecological malignancies. Int J Gynecol Cancer 2007;17:311-5.  Back to cited text no. 1
Buza N, Hui P. Immunohistochemistry in gynecologic pathology: An example-based practical update. Arch Pathol Lab Med 2017;141:1052-71.  Back to cited text no. 2
Ansari-Lari MA, Staebler A, Zaino RJ, Shah KV, Ronnett BM. Distinction of endocervical and endometrial adenocarcinomas: Immunohistochemical p16 expression correlated with human papillomavirus (HPV) DNA detection. Am J Surg Pathol 2004;28:160-7.  Back to cited text no. 3
Kar T, Kar A, Dhal I, Panda S, Biswal P, Nayak B, et al. Serous tubal carcinogenesis: The recent concept of origin of ovarian, primary peritoneal and fallopian tube high-grade serous carcinoma. J Obstet Gynaecol India 2017;67:432-41.  Back to cited text no. 4
Hu A, Li H, Zhang L, Ren C, Wang Y, Liu Y, et al. Differentiating primary and extragenital metastatic mucinous ovarian tumours: An algorithm combining PAX8 with tumour size and laterality. J Clin Pathol 2015;68:522-8.  Back to cited text no. 5
Fukunaga M. Immunohistochemical characterization of p57(KIP2) expression in early hydatidiform moles. Hum Pathol 2002;33:1188-92.  Back to cited text no. 6
Guo M, Baruch AC, Silva EG, Jan YJ, Lin E, Sneige N, et al. Efficacy of p16 and proExC immunostaining in the detection of high-grade cervical intraepithelial neoplasia and cervical carcinoma. Am J Clin Pathol 2011;135:212-20.  Back to cited text no. 7
Shi J, Liu H, Wilkerson M, Huang Y, Meschter S, Dupree W, et al. Evaluation of p16INK4a, minichromosome maintenance protein 2, DNA topoisomerase IIalpha, proEX C, and p16INK4a/ProEX C in cervical squamous intraepithelial lesions. Hum Pathol 2007;38:1335-44.  Back to cited text no. 8


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