Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium

Abstract

BackgroundThe molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses.Methodology/Principal FindingsWe studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035).ConclusionOur data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future.

Factors prognostic of survival in advanced-stage uterine serous carcinoma

“…[29] Furthermore, molecular analysis of mixed USC and endometrioid tumors has found them to more closely resemble pure USC than pure endometrioid malignancies. [30] In our study, however, mixed histology was associated with improved OS as compared with pure USC. These findings highlight the importance of careful pathologic characterization of these tumors, rather than simply defining them as USC.…”

Nestin: A biomarker of aggressive uterine cancers

“…Progestin is a therapeutic option for endometrial cancer patients who are poor surgical candidates or wish to maintain fertility [12,33], has a protective effect on the endometrium, and is also being explored for chemopreventive activity alone or in combination with vitamin D [17]. Progestin induces cellular differentiation, the mechanism by which includes suppression of TGF-β signaling and inhibition of EMT [9,10] Biomarkers assist in clinical management decision making of uterine cancer patients, distinguishing those cancers with more or less aggressive features [9][10][11][12][13][14]33].…”

“…These non-low-grade endometrioid cancers are typically more virulent and account for a disproportionate number of uterine cancer deaths [6,7]. The Cancer Genome Atlas (TCGA) Research Network and other groups are defining molecular distinctions and similarities between the different uterine cancer subtypes [8] and these biomarkers have been shown to have predictive [9] and biologic value [9][10][11][12][13][14].…”

Troponin through the looking-glass: emerging roles beyond regulation of striated muscle contraction

“…The potential involvement of Tm in these proposed mechanisms is consistent with the findings of TPM3 overexpression in online cancer databases. A separate study examining gene expression changes in human endometrial carcinoma tissue revealed that TNNT1 is differentially expressed, depending on the specific subtype of endometrial carcinoma [ 93 ].…”