IMP3 Distinguishes Uterine Serous Carcinoma From Endometrial Endometrioid Adenocarcinoma

Abstract

Differentiating uterine serous carcinoma (USC) from endometrioid adenocarcinoma (EAC) could be problematic, especially in high-grade EACs and tumors exhibiting architectural variations. To address this issue, we evaluated 103 endometrial carcinoma cases using 4 immunomarkers, beta-catenin, IMP3, PTEN, and p53. Cases included 31 USCs, 57 EACs, and 15 mixed EAC-USCs. Of 31 USCs and 57 EACs, 8 and 9, respectively, were considered diagnostically difficult and challenging. beta-catenin was more frequently expressed in EAC (P = .001); p53, PTEN, and IMP3 were more frequently found in USC (P < .001 for each). IMP3 was the best independent predictive marker for USCs. The best marker combination for predicting USCs was PTEN+/IMP3+ (exact odds ratio, 163.87; 95% confidence interval, 19.62 to infinity; P < .001). IMP3 was consistently negative in all 9 challenging EAC cases and consistently positive in all 8 challenging USC cases. None of the markers or their combinations demonstrated any value in making the diagnosis of serous component in mixed EAC-USC tumors. IMP3 immunoexpression and the IMP3+/PTEN+ pattern are the best independent and combination markers, respectively, to predict USCs. We strongly recommend using them in difficult and challenging cases.

Expression and utility of IMP3 in the differential diagnosis of atypical glandular cells and adenocarcinoma in liquid-based cervical cytology

“…Our results are consistent with those previously reported by other authors in histological studies, [12][13][14][15]19,20 where IMP3 was expressed in 90% of EC and EAIS cases, and most endometrial PSC (94%-100%) and endometrial CCC cases (57%-90%), but only a minority of EMAC (7%-25%). Nevertheless, we have noticed a trend for IMP3 to be more often expressed in EMAC with higher nuclear grade (NG 3) than those with a lower nuclear grade (NG 1 and 2).…”

“…Re-expression of IMP3 is observed in tissue sections of several human malignancies, 16 including in situ and invasive endocervical adenocarcinoma and serous and clear cell carcinoma of endometrium. [13][14][15]19,20 To our knowledge, there is little experience with the use of IMP3 in LBC cytology containing AGCs or Ac. In a small study by Lastra et al, 12 the ICC expression and utility of IMP3 and ProEx C (a monoclonal antibody cocktail shown to be positive in dysplastic squamous and endocervical lesions) were assessed in a cohort of 34 cases diagnosed as atypical glandular cells of undetermined significance (AGUS) on cytology and found that IMP3 was positive in 80% of glandular neoplasms and negative in 93% nonglandular lesions/cases negative for squamous intraepithelial lesion (SIL).…”

“…By combining the Ac in group I (19) and those in group II (23), IMP3 was expressed in 30 of 42 (71.4%) adenocarcinomas. When the two extrauterine carcinomas (1 colorectal carcinoma and 1 Paget disease) were excluded from our analysis, IMP3 was expressed in 30 of 40 (75%) of all uterine adenocarcinoma, the great majority of which (86.7%) were EAIS, EC, and type II endometrial carcinomas (PSC and CCC), whereas only 40% of EMAC were positive for IMP3.…”

Novel TP53 gene mutation and correlation with p53 immunohistochemistry in a mixed epithelial carcinoma of the endometrium

“…Endometrioid carcinoma, however, has been shown to manifest TP53 gene mutation predominantly in its later stages and in higher grade tumors (Mhawech-Fauceglia et al, 2010). Many studies have investigated either TP53 gene mutation or p53 protein expression in mixed tumors, but correlation of the two has not been well described (Koul et al, 2002).…”

The Relationship Between IMP3 Expression in Colorectal Adenocarcinoma and Clinicopathologic Findings

“…Furthermore, IMP3 or insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an RNA-binding oncofetal protein, which weighs 65 -70 KD and includes 580 amino acid and four K-homolog domains and is coded by the IMP3 gene on chromosome 7p11.5 and produces a 4350 base-pair mRNA (1,3). Overexpression of IMP3 (also known as L523S) has been reported in many cancers such as pancreatic carcinoma (4,5), lung adenocarcinoma (6-8), renal cell carcinoma (9-11), hepatocellular carcinoma, malignant melanoma (12), gastric cancer (13), ovarian carcinoma (14,15), urothelial carcinoma of bladder (16), cervical carcinoma (17,18), and testis cancer (19). It has been suggested as a prognostic marker in some cancers including breast cancer (20), neuroblastoma (21), and cervical cancer (18).…”