Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate

Abstract

Background: Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate. Methods: Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion. Results: In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised. Conclusions: Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall

“…32 All these issues raise the need for accurate immunohistochemical markers that can differentiate these two entities. 33 GATA3 is a transcription factor involved in the differentiation of multilineage epithelia including breast and urothelium, but also T lymphocytes. A The tumour was high-grade, solid, with no gland formation.…”

“…Finally, both tumours can even coexist in the same specimen, given the high frequency of PCa in elderly men being treated with cystoprostatectomy or receiving transurethral resection for urothelial carcinoma, 31 and the possibility of collision metastases to the same site 32 . All these issues raise the need for accurate immunohistochemical markers that can differentiate these two entities 33 …”

Utility of D2-40, Cytokeratin 5/6, and High–Molecular-weight Cytokeratin (Clone 34βE12) in Distinguishing Intraductal Spread of Urothelial Carcinoma From Prostatic Stromal Invasion

“…Several immunohistochemical approaches were previously proposed to solve this issue but none gained widespread acceptance in practice. [25][26][27] Lee et al 25 suggested the use of HMWCK to demonstrate the presence/absence of prostatic basal cells in conjunction with GATA-3 to stain for neoplastic urothelium to investigate for stromal invasion. However, Chastain et al 27 demonstrated strong immunoreactivity for HMWCK in basal cells in only 50% of their cohort.…”

“…In fact, prostatic basal cells and urothelium share a similar immunoprofile, which significantly complicates the assessment of equivocal lesions (especially in limited biopsies). Several immunohistochemical approaches were previously proposed to solve this issue but none gained widespread acceptance in practice 25–27. Lee et al25 suggested the use of HMWCK to demonstrate the presence/absence of prostatic basal cells in conjunction with GATA-3 to stain for neoplastic urothelium to investigate for stromal invasion.…”