Despite Diagnostic Morphology, Many Mixed Endometrial Carcinomas Show Unexpected Immunohistochemical Staining Patterns

Abstract

Historically, endometrial carcinomas have been classified primarily according to their histology. However, the use of immunohistochemistry has become commonplace in their evaluation, particularly in diagnostically challenging cases. Our objective was to evaluate mixed endometrial carcinomas using a well-established panel of biomarkers to assess the consistency and utility of these stains in clinical diagnosis. Eighteen cases comprised of various combinations of classical serous (SC), endometrioid (EC), and clear cell (CC) morphologies were identified and subjected to a panel of immunohistochemical markers including p53, p16, Ki67, estrogen receptor, progesterone receptor, and Napsin A. Intensity and extent of staining were evaluated on 4-tiered and 5-tiered scales, respectively. The typical immunostaining pattern expected for the individual tumor components was seen in only 3 cases, while in 15 cases an unexpected pattern was observed with at least one immunomarker. By tumor type, the most common unexpected finding in EC/SC carcinoma cases was diffuse positivity for p16 and/or estrogen receptor/progesterone receptor in both components, while in SC/CC, diffuse positivity for p53 in both components was most frequently seen, and in SC/CC/EC, Napsin A negativity was most commonly observed. Despite displaying diagnostic morphology, components of many mixed endometrial carcinomas may not exhibit expected immunohistochemical features. This may be due to the fact that these carcinomas arise from a single clone with subsequent divergence, resulting in a tumor with both mixed histologic and genetic features. It is important to note that these tumors may not demonstrate the immunohistochemical prototype of their constituents and should be approached accordingly from a diagnostic perspective.

<p>Researches on the Correlation Between Estrogen and Progesterone Receptors Expression and Disease-Free Survival of Endometrial Cancer</p>

“…It is well known that the two types of tumors may have different pathogenesis, In clinical practice, mixed endometrial carcinomas exist in a considerable number of tumors, or due to the heterogeneity of tumors, the diagnosis of the same tumor tissue type and grade by pathologists may be out of sync, leading to challenges in the prognosis and treatment evaluation of patient. [13][14][15][16] A recent study performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas found that 25% of high-grade endometrioid tumors and uterine serous tumors had extensive copy number alterations and low ER/PR status. However, most endometrioid tumors have almost no copy number alterations, mainly manifested by gene stabilization and estrogen signaling activation.…”

Miks endometriyal karsinomun klinik ve patolojik özelliklerinin tersiyer bir merkezde değerlendirilmesi

“…Roelofsen et al 14 showed that the prognosis for pure serous carcinomas was worse than for MECs. Matrai et al 22 immumohistochemically investigated 18 cases with MEC and they concluded that these tumors might not display the immunohistochemical prototype of their components and support for the complex evolution of mixed carcinomas. As a result of our study, we can say that, in the presence of more than 5% type 2 components, the prognosis is not different from those with pure type 2 endometrial carcinoma.…”

A “Null” Pattern of p16 Immunostaining in Endometrial Serous Carcinoma: An Under-recognized and Important Aberrant Staining Pattern

“…Fadare et al 39 showed that a wild-type p53 staining result does not necessarily exclude SC in the correct clinical and morphologic setting and even demonstrated that such cases may still harbor pathogenic TP53 mutations. Matrai et al 40 demonstrated that in some cases of mixed SC/HGEC, the HGEC component can show a SC-like diffuse pattern of p16 expression.…”

“…Fadare et al (39) showed that a wild-type p53 staining result does not necessarily exclude SC in the correct clinical and morphologic setting and even demonstrated that such cases may still harbor pathogenic TP53 mutations. Matrai et al (40) demonstrated that in some cases of mixed SC/HGEC, the HGEC component can show a SC-like diffuse pattern of p16 expression. We recommend that a completely negative (null) p16 staining result, in the presence of appropriately staining internal controls, when encountered in the setting of an otherwise classical clinicopathologic picture of SC (i.e.…”