GATA3 Positivity Research Articles

GATA-3 Expression in all Grades and Different Variants of Primary and Metastatic Urothelial Carcinoma.

Urothelial carcinoma has a varied and wide histological spectrum posing a diagnostic challenge in H&E examination alone. Immunohistochemical markers like GATA-3 along with other appropriate panel of IHC can be used. However, the percentage positivity and its intensity may vary in different variants and grades of primary and metastatic urothelial carcinoma. To observe the GATA-3 expression patterns in all the grades and different variants of primary and metastatic urothelial carcinomas. It is a prospective and retrospective observational study. All the clinically suspected urothelial carcinoma (UC) during January 2016 to December 2017 were included in the study. Depending on the differential diagnosis considered, immunohistochemistry (IHC) markers including CK7, CK20, p63, AMACR, CDX2, and p16 were done to differentiate UC from other primary carcinomas. The tumors confirmed as UC were analyzed further for GATA-3 expression by Chi-square test. The number of UC in the present study was 126 including 122 (bladder in 107, ureter in 7, renal pelvis in 5, and urethra in 3) primary and 4 metastatic UC (3 in lung and 1 in liver). Age of the patients ranged from 29 to 80 (mean 61.28) years with male/female ratio 4:1. GATA-3 showed positivity in 97 (79.5%) primary UC. GATA-3 was positive in all normal urothelium and non-invasive UC (100%), while it was positive in 69/94 (73.4%) invasive UC including variants. GATA-3 was positive in 35/39 LP invasive (89.74%) and 34/55 (61.81%) MP invasive UC. GATA-3 was positive in 39/40 papillary cases (97.5%) and 45/59 (76.27%) cases of non-papillary UC. GATA-3 showed strong expression in all metastatic UC (100%). GATA-3 expression was seen in 101/126 (80.15%) of UC including primary and metastatic carcinomas and hence was a useful marker in diagnosing UC. The GATA-3 positivity decreased from normal urothelium to UC; low-grade UC to high-grade UC; non-invasive to invasive UC; lamina propria invasive to muscle invasive UC; papillary to non-papillary UC.

GATA3 expression in the solid cell nest of thyroid.

Solid cell nest (SCN) of thyroid is a benign histomorphological mimicker of papillary microcarcinoma. Previous studies have elucidated a few immunohistochemical markers of SCN that aid in its distinction from papillary microcarcinoma. The positivity of GATA3 in SCN has been demonstrated only recently. We also document GATA3 positivity in three cases of SCN.

Incidence and Significance of GATA3 Positivity in Pancreatic Ductal Adenocarcinoma and Cholangiocarcinoma.

GATA3 is a transcription factor involved in the development and differentiation of lymphocytes, breast, and hair follicles. The protein is a useful immunohistochemical (IHC) marker for supporting diagnoses of breast or urothelial carcinoma. This can be especially helpful in metastatic neoplasms to help delineate site of origin. GATA3 is also reportedly positive in a percentage of pancreatic ductal adenocarcinomas (PDACs) and cholangiocarcinomas (CCs), but no study has closely evaluated this relationship with respect to clininopathologic features or patient outcome. Using tissue microarrays, we analyzed 240 PDACs and 60 CCs with GATA3 IHC and compared expression to various clinical and pathologic parameters. Overall, GATA3 positivity was seen in 16% of PDACs and 5% of CCs. GATA3 positivity in PDAC cases was more common in male patients (P=0.013). GATA3-positive PDACs trended toward worse survival on multivariate analysis (P=0.074). The only 3 GATA3-positive CCs were poorly differentiated (P=0.069); low case number precluded multivariate survival analysis for CCs. GATA3 positivity can occur in carcinomas of the pancreatobiliary system, which should be considered during IHC workup of neoplasms of unclear origin. This positivity seems to have minimal relevance to patient outcome.

GATA3 Immunohistochemical Staining in Hodgkin Lymphoma: Diagnostic Utility in Differentiating Classic Hodgkin Lymphoma From Nodular Lymphocyte Predominant Hodgkin Lymphoma and Other Mimicking Entities.

Classic Hodgkin lymphoma (CHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) are clinically distinct entities, with different prognostic and treatment implications. In addition, several large B-cell lymphomas and some T-cell lymphomas can mimic CHL. Differentiating these entities from CHL is crucial for ensuring appropriate therapy. GATA3 is a T-cell transcription factor involved in T-cell maturation and has been previously shown to be overexpressed in CHL cells via gene expression profiling. We investigated the utility of GATA3 immunostain in differentiating CHL from NLPHL and other mimicking entities. We accrued 17 NLPHLs, 49 CHLs [23 nodular sclerosis (NS), 3 syncytial variants, 3 lymphocyte rich and 13 mixed cellularity types], 4 primary mediastinal large B-cell lymphomas (PMBLs), 2 Epstein-Barr virus (EBV) positive diffuse large B-cell lymphomas (DLBCLs) (EBV+LBCLs), 2 T-cell/histiocyte-rich large B-cell lymphomas (TCHRBCLs), 1 gray zone lymphoma, and 2 tissue microarrays consisting of 72 DLBCLs. One slide from each was stained with GATA3 and percent positive tumor cells and intensity of nuclear expression was semiquantitatively graded independently by 2 board certified hematopathologists. GATA3 was positive in 80% of CHLs. Both percent positivity and intensity of staining varied greatly. Syncytial variant of NS subtype showed the highest positivity rate (3/3; 100%), followed by NS (20/23; 87%), mixed cellularity (9/13; 70%), and lymphocyte rich (2/3; 67%). GATA3 was negative in all NLPHLs, EBV+LBCLs, TCRBCLs, and DLBCLs stained. The single gray zone lymphoma and 3/4 PMBLs were positive. Nuclear expression of GATA3 can be used to delineate CHL from NLPHL. GATA3 positivity effectively excludes NLPHL with 100% negative predictive value. However, as 20% of CHL can be negative for GATA3, CHL cannot be ruled out with negative GATA3. Additional findings include GATA3 positivity among PMBLs, whereas all 72 DLBCLs were negative for GATA3. This finding further highlights similarities between CHL and PMBL.

Urothelial tumors with villous morphology: Histomorphology and role of immunohistochemistry in diagnosis.

Villous adenoma and urothelial carcinoma with villoglandular differentiation (UCVGD) are rare urothelial tumours showing villous morphology, the former being a preneoplastic entity and the latter being a malignant one. The detailed immunohistochemistry of these entities is previously not described in the literature. Moreover, a limited biopsy sample of UCVGD or a villous adenoma with or without adenocarcinoma may be difficult to distinguish on the basis of the histomorphology alone. An immunohistochemical panel comprising of GATA3, p63, β-catenin, CK7 and CK20 was performed on five cases of UCVGD and three cases of villous adenoma with the aim of studying the expression of the proteins thereby aiding in the diagnosis of these entities in a limited surgical pathology specimen. The mean age of UCVGD was 66.8 years and all the patients were male. All the cases of UCVGD were associated with high grade papillary urothelial carcinoma with lamina propria invasion. The immunohistochemical panel showed strong nuclear GATA3 expression in the urothelial component of UCVGD. Interestingly, the high grade and the low grade villoglandular components of UCVGD also expressed GATA3 (nuclear) with a progressive loss of expression from the high grade to the low grade component. The villous adenomas showed negativity or aberrant cytoplasmic positivity for GATA3. The β-catenin showed a gradual loss of membranous expression from villous adenoma to low grade and high grade villoglandular components of UCVGD with a patchy membranous expression in the urothelial component of the UCVGD. p63 showed strong nuclear positivity in the urothelial component and uniform negativity in the villous adenoma and villoglandular component of UCVGD irrespective of its grade, thereby distinguishing the villoglandular component from the urothelial component. The urothelial component of UCVGD showed strong membranous CK7 expression and was higher than the CK20 expression in the urothelial component. In contrast, CK20 expression was higher in villous adenoma as compared to CK7. There was no difference in the expression of CK7 and CK20 in the villoglandular components and low grade and high grade villoglandular areas. The above-mentioned immunohistochemical pattern may help to distinguish the UCVGD from the villous adenoma.

Positivity for GATA3 and TTF-1 (SPT24), and Negativity for Monoclonal PAX8 Expand the Biomarker Profile of the Solid Cell Nests of the Thyroid Gland.

Solid cell nests (SCNs) are usually distinguished on conventional H&E-stained sections; however, the morphological heterogeneity in SCNs and hyperplasia of these ultimobranchial body remnants can mimic other diagnostic entities including but not limited to papillary microcarcinoma. In order to confirm the thyroid follicular epithelial origin and exclude the possibility of SCNs, most diagnosticians use immunohistochemical biomarkers of thyroid follicular epithelial cells and/or those of SCNs. While the expression profile of monoclonal PAX8 has not been reported previously in SCNs, the status of TTF-1 expression using the 8G7G3/1 clone has been inconsistent among several studies. Given the potential diagnostic pitfalls, this series investigated the expression profile of GATA3, monoclonal PAX8, and TTF-1 (SPT24), along with p63, p40, monoclonal calcitonin, monoclonal CEA, and HBME-1 in a tissue microarray (TMA) of 56 SCNs. SCNs were all diffusely and strongly positive for TTF-1 (SPT24), p63, and p40, and were negative for monoclonal PAX8 and calcitonin. Positivity for GATA3 and monoclonal CEA was identified in 41 (73.2%) and 36 (64.3%) of SCNs. In addition, 18 (32.1%) SCNs displayed HBME-1 reactivity. These findings expand the immunohistochemical correlates of SCNs by demonstrating positivity for GATA3 and TTF-1 (SPT24), and negativity for monoclonal PAX8. The identification of monoclonal CEA expression and HBME-1 in SCNs also underscores the limitations of these select biomarkers in the distinction of C cell proliferations and papillary microcarcinoma, respectively. The findings of this series also suggest that positivity for TTF-1 (SPT24) alone should not be used to confirm the thyroid follicular epithelial origin. Therefore, the combined use of TTF-1 (SPT24) and monoclonal PAX8 in association with p63 or p40 provides an accurate distinction of SCNs.

Vasitis nodosa and related lesions: a modern immunohistochemical staining profile with special emphasis on novel diagnostic dilemmas

Vasitis nodosa is a benign proliferation of vas deferens epithelium, thought to be a response to trauma or obstruction, usually vasectomy. Although histologic features mimic malignancy, diagnosis is usually straightforward due to the clinical context. We analyzed 21 specimens with vasitis or epididymitis nodosa with antibodies to PAX8, CD10, p63, α-methyl-acyl-coA-racemase (AMACR), GATA3, prostein, NKX3.1, and prostate-specific antigen (PSA). Two diagnostically problematic cases included (1) florid bladder muscle involvement after prostatectomy and (2) involvement of the ampulla and ejaculatory duct in a radical prostatectomy specimen. Vasitis nodosa was excluded in 3 additional histologic mimics (2 post-treatment prostate cancers and 1 bladder cancer). PAX8 yielded consistent positive (100%) nuclear staining in the proliferative glands of vasitis nodosa, often stronger and more uniform than native vas deferens. CD10 labeling was common but also labeled secretions and other structures. Labeling for p63 was often basally located in glands with a multilayered appearance, but often markedly attenuated or lacking in the proliferative glands compared to native epithelium. AMACR positivity was variable but often present (19/21). PSA, prostein, and NKX3.1 were consistently negative. Rare problematic cases of vasitis nodosa include "invasion" of the ejaculatory duct at the prostate and involvement of bladder muscle after prostatectomy. The proliferative vasitis nodosa glands often have a prostate cancer-like staining pattern with variable AMACR positivity and negative or patchy p63. However, reliable positivity for PAX8, patchy GATA3, and negative staining for PSA, NKX3.1, and prostein aid in distinguishing from prostate cancer and tubular variants of bladder cancer.

Utility of different immunostains for diagnosis of metastatic breast carcinomas in both surgical and cytological specimens.

A panel of immunostains is usually performed to confirm a metastatic carcinoma origin. GATA3 is a transcription factor and has been proven to be a useful marker for breast carcinoma. Other immunostains including mammaglobin (MGB), gross cystic disease fluid protein 15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) are also used in diagnosing metastatic breast cancer. In this study, we aimed to compare the performance of these immunostains in the work up of metastatic breast carcinoma in both surgical and cytological specimens. This study cohort was composed of 242 metastatic breast carcinomas (142 surgical and 100 cytological specimens) during a study period from October 2013 to December 2015. Immunostain results of GATA3, CK7, MGB, GCDFP-15, ER and PR and their correlations were examined. In surgical specimens, GATA3 and CK7 were highly expressed (88% and 87%), but MGB and GCDFP-15 showed much lower positivity rates (43% and 29%). In cytological specimens, GATA3, CK7 and MGB showed similar positivity rates to those in surgical specimens; but GCDFP-15, ER and PR showed significantly lower positivity rates than those in surgical specimens. All ER-positive cases were positive for GATA3 in both surgical and cytological specimens; however, GATA3 positivity showed a significantly stronger correlation with ER positivity in surgical specimens than in cytological specimens. GATA3 and CK7 performed better than other immunostains to detect metastatic breast carcinoma in both surgical and cytological specimens. GATA3 expression was positively correlated with ER expression, and the correlation was stronger in surgical specimens than in cytological specimens.

GATA3 expression in benign prostate glands with radiation atypia: a diagnostic pitfall.

Patients who have undergone prostate radiation are at increased risk for developing urothelial carcinoma. Radiation changes can cause significant cytological atypia in benign prostate glands that may mimic pagetoid spread of urothelial carcinoma. GATA3 is a common marker for differentiating prostatic adenocarcinoma from urothelial carcinoma. The aim of this study was to investigate the expression of GATA3 in the epithelium of irradiated benign and malignant prostate tissue. We performed a retrospective review of prostate cases with radiation atypia. GATA3 staining was performed on benign prostate tissue with and without radiation atypia, as well as on residual/recurrent prostatic adenocarcinoma after radiation therapy. PIN4 immunohistochemical (IHC) staining was performed on prostate tissue with radiation atypia to confirm the presence of both basal and luminal cells. We identified 31 cases with benign prostate glands containing radiation atypia. The average time between treatment with radiation therapy and the surgical procedure was 10 years (range 5-20 years). PIN4 IHC staining confirmed the presence of basal and luminal cells in benign prostate glands with radiation atypia. Thirty-one of 31 (100%) cases of benign prostate tissue with radiation atypia showed staining for GATA3 in both basal and luminal cells. Eight of eight (100%) cases of benign prostate glands without radiation atypia and no inflammatory changes showed GATA3 positivity limited to basal cells. GATA3 was negative in 12/12 (100%) cases of prostatic adenocarcinoma after radiation therapy. Benign prostate glands with radiation atypia show diffuse positivity for GATA3. This staining pattern, along with the cytological atypia resulting from radiation, can mimic urothelial carcinoma.

GATA3 immunohistochemistry in urothelial carcinoma of the upper urinary tract as a urothelial marker and a prognosticator

Immunohistochemistry of a transcription factor, GATA3, has been widely used as a promising urothelial marker in diagnostic surgical pathology practice. However, the expression status of GATA3 in upper urinary tract urothelial carcinomas (UUTUCs) and its prognostic significance have not been fully investigated. We immunohistochemically stained for GATA3 in 99 UUTUC samples and paired nonneoplastic urothelial tissues. GATA3 was positive in 51 (51.5%; 32 [32.3%] weak, 11 [11.1%] moderate, 8 [8.1%] strong) of 99 UUTUCs, which was significantly lower than in benign urothelium (79 [96.3%] of 82; 33 [40.2%] weak, 35 [42.7%] moderate, 11 [13.4%] strong; P<.001). However, there were no statistically significant associations between GATA3 expression and tumor grade, pT stage, lymph node involvement, or distant metastasis. Meanwhile, the rate of GATA3 positivity was significantly higher (P=.004) in ureteral tumors (66.0%) than in renal pelvic tumors (35.6%). Kaplan-Meier and log-rank tests revealed that GATA3 negativity was significantly associated with lower recurrence-free survival (P=.037 for all cases, P=.026 for muscle-invasive tumors) and cancer-specific survival (P=.007 for all cases, P=.012 for muscle-invasive tumors, P=.035 for cases with adjuvant chemotherapy) rates. Multivariate analysis further identified strong correlations of GATA3 expression with tumor progression (all cases: hazard ratio [HR], 0.479 [95% confidence interval {CI},0.229-1.003; P=.051]; muscle-invasive tumors: HR, 0.387 [95% CI, 0.166-0.903; P=.028) or cancer-specific mortality (all cases: HR, 0.354 [95% CI, 0.135-0.925; P=.034]; muscle-invasive tumors: HR, 0.402 [95% CI, 0.149-1.086; P=.072]). Thus, compared with nonneoplastic urothelium, a significant decrease in the expression of GATA3 in UUTUC was seen. Moreover, loss of GATA3 expression was found to be an independent predictor of poor patient outcomes. Of note was that only roughly half of high-grade and/or muscle-invasive UUTUCs were immunoreactive for GATA3.

GATA3 Positivity in Benign Radiated Prostate Glands: A Potential Diagnostic Pitfall.

Histologic changes following radiation therapy to the prostate include multilayering of glands, atrophy, squamous metaplasia, and often marked random nuclear atypia. We have seen multiple consultation cases where the differential diagnosis of these radiated prostate glands included urothelial carcinoma, with multilayered to solid-appearing proliferations that were positive by immunohistochemistry for GATA3. To formally investigate this issue, 30 cases of benign prostate tissue with radiation atypia, from 1990 to 2015, were obtained from our institution. Cases were evaluated by immunohistochemistry for the prostate-specific markers prostate-specific antigen (PSA), P501S (Prostein), and NKX3.1 and urothelial markers GATA3 and uroplakin 2. GATA3 was positive in 100% of cases, with 70% showing moderately strong to strong staining in a mostly patchy manner within a gland. PSA was positive in 93.3% of cases, with 89.2% showing moderately strong to strong staining in a mostly diffuse manner. P501S was positive in 96.7% of cases, with 93.1% showing moderately strong to strong staining in a mostly patchy manner. NKX3.1 was positive in 82.8% of cases, with 33.3% showing moderately strong to strong staining in a mostly patchy manner. Uroplakin 2 was negative in 100% of cases. Our findings highlight that GATA3 is often positive in benign prostate glands with radiation atypia, which along with the morphologic features present a pitfall for the misdiagnosis of urothelial carcinoma. A combination of PSA and P501S is the best prostate-specific panel for use in radiated prostate, with the caveat that they are often patchy and do not stain all radiated glands.

MP71-04 GATA3 IMMUNOHISTOCHEMISTRY IN UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT AS A UROTHELIAL MARKER AS WELL AS A PROGNOSTICATOR

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I1 Apr 2017MP71-04 GATA3 IMMUNOHISTOCHEMISTRY IN UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT AS A UROTHELIAL MARKER AS WELL AS A PROGNOSTICATOR Satoshi Inoue, Kazutoshi Fujita, Hiroki Ide, Seiji Yamaguchi, Hiroaki Fushimi, George Netto, Norio Nonomura, and Hiroshi Miyamoto Satoshi InoueSatoshi Inoue More articles by this author , Kazutoshi FujitaKazutoshi Fujita More articles by this author , Hiroki IdeHiroki Ide More articles by this author , Seiji YamaguchiSeiji Yamaguchi More articles by this author , Hiroaki FushimiHiroaki Fushimi More articles by this author , George NettoGeorge Netto More articles by this author , Norio NonomuraNorio Nonomura More articles by this author , and Hiroshi MiyamotoHiroshi Miyamoto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2260AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A transcription factor, GATA3, has been one of the most useful urothelial markers in diagnostic surgical pathology practice. However, previous studies have assessed the utility of GATA3 immunohistochemistry often in bladder specimens. Moreover, the prognostic significance of GATA3 expression in upper urinary tract urothelial carcinomas (UUTUCs) has not been fully investigated. Meanwhile, using cell line and animal models, we have demonstrated that GATA3 functions as a tumor suppressor for urothelial cancer. The current study aims to determine the expression status of GATA3 in UUTUC and its prognostic significance. METHODS We immunohistochemically stained for GATA3 in the tissue microarrays consisting of 99 UUTUC samples and paired non-neoplastic urothelium from each case. We then evaluated the associations between GATA3 expression and clinicopathologic features available for our patient cohort. RESULTS GATA3 was positive in 51 [52%; 32 (32%) weak, 11 (11%) moderate, 8 (8%) strong] of 99 UUTUCs, which was significantly lower than in benign urothelium [79 (96%) of 82; 33 (40%) weak, 35 (43%) moderate, 11 (13%) strong] (P < 0.001). Ten (67%) of 15 low-grade versus 41 (48%) of 84 high-grade UUTUCs (P = 0.266) and 20 (54%) of 37 non-muscle-invasive versus 31 (50%) of 62 muscle-invasive UUTUCs (P = 0.836) were immunoreactive for GATA3. There were also no statistically significant associations between GATA3 expression and pN status, distant metastasis, gender of the patients, or the side of UUTUC. However, the rate of GATA3 positivity was significantly higher (P = 0.004) in ureteral tumors (66%) than in renal pelvic tumors (36%). Kaplan-Meier and log-rank tests revealed that GATA3 negativity significantly correlated with lower recurrence-free survival (P = 0.040 for all cases; P = 0.030 for muscle-invasive tumors) and cancer-specific survival (P = 0.007 for all cases; P = 0.012 for muscle-invasive tumors) rates. Multivariate analysis further identified strong correlations of GATA3 expression with cancer-specific mortality of all cases [hazard ratio (HR) = 0.399, 95% confidence interval (CI) = 0.179-0.890, P = 0.025] or muscle-invasive tumors (HR = 0.374, 95% CI = 0.169-0.831, P = 0.016). CONCLUSIONS Compared with non-neoplastic urothelium, a significant decrease in the expression of GATA3 in UUTUC was seen. Of note was that GATA3 was immunohistochemically detected only in roughly half of high-grade and/or muscle-invasive UUTUCs. In addition, loss of GATA3 expression was found to be an independent predictor of poor patient outcomes. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e945-e946 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Satoshi Inoue More articles by this author Kazutoshi Fujita More articles by this author Hiroki Ide More articles by this author Seiji Yamaguchi More articles by this author Hiroaki Fushimi More articles by this author George Netto More articles by this author Norio Nonomura More articles by this author Hiroshi Miyamoto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinicopathologic features of mammary analogue secretory carcinoma of salivary glands

Objective: To investigate the clinicopathological features of mammary analogue secretory carcinoma (MASC) of salivary glands, and its diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Seventeen cases of MASC were enrolled, with 9 cases of salivary acinar cell carcinoma and 18 cases of adenoid cystic carcinoma as control groups from Nanjing General Hospital from 1997 to 2014 were included in this retrospective study, combined with immunohistochemistry and molecular detection of ETV6-NTRK3 gene fusion. All cases were histologically reviewed with immunohistochemical staining (EnVision) for S-100 protein, SOX10, GATA3, CD117 expression in each group. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion. Results: The age of MASC patients ranged from 27 to 74 years with mean age of 47 and ratio of male and female was 4∶3. All cases showed infiltrative growth and diverse cytology and histology, including lobular (8 cases), cystic papillary (3 cases), cribriform mixed with papillary and glandular structures (6 cases) at various proportions. Some tumors of MASC also exhibited solid growth areas with occasional microcystic honeycombed pattern composed of small cysts merged into larger cysts resembling thyroid follicles. S-100 protein and SOX10 were strongly positive in all MASC cases (17/17). In addition, there was insignificant positivity for GATA3 (3/17) and CD117 (4/17). ETV6 gene fusion detection was informative in 12 MASC cases by FISH with 10 positive cases and 2 negative cases. Conclusions: Combined immunohistochemical positivity of S-100 protein, CD117 and SOX10 are useful in the diagnosis and differential diagnosis of MASC. FISH detection of ETV6-NTRK3 fusion offers an additional molecular diagnostic marker for the diagnosis.

GATA-3 expression is not associated with complete pathological response in triple negative breast cancer patients treated with neoadjuvant chemotherapy

ObjectiveThe prognosis for patients with triple negative breast cancer (TNBC) is poor, however, a subset will demonstrate complete pathological response (pCR) to chemotherapy. GATA-3 and AR may be a negative predictors for pCR although it is unclear if these results apply to TNBC. MethodsPatients diagnosed with TNBC and treated with neoadjuvant chemotherapy were identified. Immunohistochemistry was performed for GATA-3 and AR. Both were scored using a composite of staining intensity and percentage cells stained. The primary outcome was pCR. ResultsTwenty-four patients were included and 7 achieved pCR. There was no difference in the pre-chemotherapy tumor size (44±28mm vs. 54±30mm; p=0.764) or lymph node status (86% vs. 71%; p=0.629) between patients with and without pCR. GATA-3 expression was present in 20 cases (83%) while AR was present in 6 cases (25%). No AR expression was seen in 15 cases (63%) with GATA-3 positivity. There was no difference in either GATA-3 (4.3±2.7 vs. 3.6±2.5; p=0.549) or AR (1.4±2.5 vs. 1.1±2.4; p=0.778) expression between patients with and without pCR. ConclusionsGATA-3 expression is frequent in TNBC even in the absence of AR. However, neither GATA-3 nor AR are associated with pCR after neoadjuvant chemotherapy.

Cytokeratin 7-negative mammary Paget's disease: A diagnostic pitfall

Pathologists should be aware of the existence of a rare CK7-negative variant of breast carcinoma in general, and of Paget's disease in particular. Cytokeratin 7-negative Paget's disease and CK7-negative ductal intraepithelial neoplasia (ductal carcinoma in situ) present a major diagnostic challenge for pathologists since there is limited awareness of their existence. When there is classic Paget's morphology on H&E sections, GATA3 positivity should resolve any doubts about the diagnosis in the setting of a CK7-negative neoplastic cell population.

Intrathyroidal Clear Cell Tumor of Parathyroid Origin with Review of Literature.

Water-clear cell adenoma (WCCA) of the parathyroid gland is an exceedingly rare neoplasm. To date, 17 cases have been reported in the literature, with only one of them being intrathyroidal. Here we report a case of a 34-year-old woman who presented for evaluation of a goiter and was found to have a thyroid nodule and abnormal thyroid function tests (TFT). Fine needle aspiration biopsy of the nodule revealed thyroid follicular cells without atypia and subsequent Afirma® Gene Expression Classifier (GEC) testing results were suspicious for malignancy. As a result, the patient underwent a right thyroid lobectomy and isthmusectomy. Histological sections revealed an intrathyroidal nodule consistent with a clear cell neoplasm of parathyroid origin. The histologic appearance together with the immune profile was diagnostic of WCCA, with diffuse positivity for GATA3, focal weak positivity for parathyroid hormone, and negativity for PAX8, thyroglobulin, TTF1, synaptophysin, chromogranin, and S100p. Our study focuses on the clinical presentation, current management strategies, and review of the available literature surrounding this rare diagnosis. The ultimate goal is to help endocrinologists and surgeons establish a foundational treatment plan for intrathyroidal clear cell tumor cases.

Immunohistochemical staining characteristics of nephrogenic adenoma using the PIN-4 cocktail (p63, AMACR, and CK903) and GATA-3.

Nephrogenic adenoma (NA) is a benign lesion of the urinary tract associated with injury to the urothelium. The varied morphologic patterns of NA make it a potential diagnostic pitfall, because it can mimic closely prostatic adenocarcinoma and urothelial carcinoma. In current practice, an antibody cocktail comprising p63, CK903, and AMACR (PIN-4 cocktail) is frequently utilized to evaluate foci suspicious for prostatic adenocarcinoma. Although the staining characteristics of the individual components of the PIN-4 cocktail have been reported for NA, no study has described the expression patterns for NA when the stains are applied as a cocktail. GATA-3 is an emerging marker of urothelial carcinoma; however, the GATA-3 staining characteristics of NA have yet to be described. Sixty-three NA specimens (M:F=36:27, average age=51.4 y) from various locations in the urinary tract including urinary bladder (n=40), ureter (n=3), and urethra (n=20) were collected from the archives of 2 institutions. Immunohistochemical analysis with the PIN-4 cocktail and GATA-3 antibodies was performed, and the distribution and intensity of staining was recorded for each antibody in each case. PIN-4 cocktail staining revealed AMACR expression in 56% of cases, CK903 expression in 97%, and rare p63 positivity (in only 2 cases). Only 2 NA cases displayed an overall PIN-4 staining pattern compatible with prostate cancer. GATA-3 expression was noted in 40% of NAs. No correlation between AMACR, CK903, or GATA-3 positivity and histologic pattern or anatomic location was identified. Although heterogenous staining patterns were seen within individual cases, use of the PIN-4 cocktail effectively discriminates NA from prostate cancer because of the high frequency of coexpression of AMACR and CK903 within NA. In addition, GATA-3 is not a useful marker in differentiating between NA and urothelial carcinoma.

GATA3 expression in small cell carcinoma of bladder and prostate and its potential role in determining primary tumor origin.

GATA3 is a sensitive marker for urothelial carcinoma. We here evaluate, for the first time, GATA3 expression in small cell carcinoma of bladder and prostate and assess its utility in the differential diagnosis with small cell carcinoma of lung primary. Archival tissues from 60 small cell carcinomas (12 bladder, 15 lung, and 33 prostate primary cases) were used to build 2 tissue microarrays. We also assessed whole slide sections from 10 additional primary small cell carcinomas of bladder. GATA3 nuclear expression was evaluated using standard immunohistochemistry. Intensity (weak, moderate, and strong) and extent of expression were assessed in each tissue microarray spot. Extent positivity was categorized as focal (1%-25%), multifocal (>25%), and diffuse (>75%). Nuclear GATA3 expression was encountered in 7 bladder (7/22, 32%) and 2 lung (2/15, 13%) small cell carcinomas. All 33 primary prostate small cell carcinomas were negative. Among bladder tumors, strong and diffuse (>75%) GATA3 labeling was seen in 3 cases (3/22, 14%); focal positivity was observed in the 4 remaining cases (4/22, 18%). Both positive lung cases had only focal positivity. Our study is the first to reveal GATA3 expression in the small subset of lung small cell carcinoma that should be taken into consideration in assigning site of origin in advanced small cell carcinoma cases. Our novel finding of GATA3 positivity in one-third of bladder small cell carcinoma is of potential value in differentiating small cell carcinomas of prostate origin from those of bladder origin.

Significance of GATA-3 expression in outcomes of patients with breast cancer who received systemic chemotherapy and/or hormonal therapy and clinicopathologic features of GATA-3–positive tumors

GATA-3 and estrogen receptor (ER) are involved in a positive cross-regulatory loop and are frequently coexpressed in breast cancers. GATA-3 expression was shown to be an independent predictor of overall and disease-free survival in some studies, whereas others showed no difference. However, the studies used different cutoff values for determining GATA-3 positivity and analyzed outcomes in patients who received systemic therapy together with those who did not. We investigated GATA-3 expression and correlated clinicopathologic findings and outcomes in 516 women who received systemic chemotherapy and/or hormonal therapy. Nuclear staining of 1% or greater was considered positive for GATA-3, ER and progesterone receptor (PR). Of 516 cases, 436 (84.5%) were GATA-3+. GATA-3+ tumors were more likely to be grade 1 or 2, ER+, PR+, non-triple-negative phenotypes (all P < .0001), and higher stage (P = .01). ER-/GATA-3+ tumors, compared with ER-/GATA-3- tumors, had worse breast cancer survival (BCS) (P = .02) and a trend for worse overall survival (OS) (P = .05) in univariate analysis. However, there was no difference in OS and BCS between patients who received chemotherapy and/or hormonal therapy among GATA-3-positive and GATA-3-negative groups. GATA-3+ tumors are correlated with lower grade, ER+, PR+, and non-triple-negative phenotypes. Although there was no difference in OS and BCS between GATA-3-positive and GATA-3-negative groups, there was an adverse effect of GATA-3 expression in the ER-negative subgroup of patients who received systemic therapy.

Use of PAX8 and GATA3 in diagnosing sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma

Immunohistochemistry for PAX8 and GATA3 are sensitive markers for renal cell carcinoma and urothelial carcinoma, respectively. However, there are limited data on these markers in sarcomatoid renal cell carcinoma (SARCRCC) and sarcomatoid urothelial carcinoma (SARCUC). Tissue microarrays (TMAs) were constructed from 45 cases of SARCRCC and 45 cases of SARCUC of the lower urinary tract, with an additional 11 SARCUCs of the upper tract. PAX8 and GATA3 were also evaluated in TMAs from 161 sarcomas from other sites, 14 atypical epithelioid angiomyolipomas (AMLs) of the kidney, 23 bladder inflammatory myofibroblastic tumors (IMTs), and 2 bladder and 4 renal leiomyosarcomas. In the SARCRCC, PAX8 and GATA3 were positive in the sarcomatoid areas in 31 (69%) and 0 (0%) of cases, respectively. In the bladder SARCUC, GATA3 and PAX8 were positive in 14 (31%) and 2 (4%) of cases, respectively. Of the 11 SARCUCs of the upper urinary tract, 2 (18%) cases were PAX8 positive and 2 (18%) separate cases were GATA3 positive. Only 1 tumor present on the sarcoma TMAs, a Ewing sarcoma/primitive neuroectodermal tumor, was PAX8 positive, and all sarcomas were GATA3 negative. Of the AMLs, IMTs, and leiomyosarcoma, only 1 case of IMT showed moderate GATA3 positivity, and all were negative for PAX8. PAX8 can be used to distinguish SARCCRCC from atypical epithelioid AMLs and primary renal or retroperitoneal sarcomas. However, in a kidney/renal pelvic tumor, PAX8 shows overlap in staining between SARCUC and SARCRCC. GATA3 lacks sensitivity but is more specific for SARCUC.