{"title":"Tissue Factor Pathway Inhibitor-2 Expression in Uterine Cervical Clear Cell Carcinoma: A Potential Biomarker for Clinical Diagnosis.","authors":"Ryuji Kawaguchi, Tomoko Uchiyama, Sumire Sugimoto, Junya Kamibayashi, Motoki Matsuoka, Tomoka Maehana, Naoki Kawahara, Yuki Yamada, Fuminori Kimura","doi":"10.1097/PAI.0000000000001270","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001270","url":null,"abstract":"<p><p>Cervical clear cell carcinoma (CCCC) is an extremely rare histologic type of uterine cancer. Tissue factor pathway inhibitor-2 (TFPI2) is a serine protease inhibitor that was recently shown to be expressed in ovarian clear cell carcinoma and endometrial clear cell carcinomas using immunohistological analyses. In this exploratory study, we conducted an immunohistochemical investigation to determine whether TFPI2 is expressed in cervical cancers, especially CCCC. Further, we examined the expression of hepatocyte nuclear factor 1 homeobox B (HNF-1β), a useful marker for immunohistological diagnosis of ovarian clear cell carcinoma. As a control group, we included 22 patients with cervical intraepithelial neoplasia grade 3 (CIN 3) and 40 patients with non-CCCC (21 with squamous cell carcinoma and 19 with adenocarcinoma). Immunohistochemical staining was positive for TFPI2 in all 3 CCCC cases (100%), whereas in non-CCCC, we observed only weak TFPI2 staining in 7 squamous cell carcinoma cases (33.3%), absence of staining in adenocarcinoma (0%), and staining in one CIN 3 case (4.5%). The histoscore for TFPI2 in CCCC was 166.7 ± 13.2 (mean ± SD), which was significantly higher than that in non-CCCC (3.3 ± 8.3) or CIN 3 (1.4 ± 6.4) (P<0.001). Similarly, HNF-1β staining was noted in all 3 CCCC cases and in 63.2% of the adenocarcinomas, whereas it was absent in CCCC and CIN 3. In conclusion, examination of TFPI2 expression, similar to that of HNF-1β, is useful for validating the immunohistological diagnosis of CCCC.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deciphering the Molecular Landscape of Urothelial Carcinoma: Immunohistochemistry-based Subtyping Using 4 Easily Available Antibodies for Cost-effective Stratification.","authors":"Shreeya Indulkar, B Vishal Rao, Debasmita Das, Mohan Krishna Pasam, Suseela Kodandapani, Rakesh Manilal Sharma, Subramanyeshwar Rao Thammineedi","doi":"10.1097/PAI.0000000000001272","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001272","url":null,"abstract":"<p><p>Molecular subtyping, though complex and typically reliant on costly and limited accessibility techniques, remains crucial for understanding the biology of urothelial carcinoma (UC). We sought a practical alternative by categorizing UCs into immunohistochemistry (IHC) subtypes using a panel of accessible antibodies. Examining 100 UCs from 2020 to 2021, encompassing both chemotherapy-naïve MIBC and NMIBC, acquired through transurethral resection or radical resection, we employed IHC with GATA3, KRT5, KRT14, and KRT20 markers on tissue microarrays. IHC luminal, IHC basal, IHC dual-positive, and IHC dual-negative subtypes were identified based on marker expressions. Positive staining criteria were established, considering >20% positive staining for specific markers. Results indicated a mean age of 64 years, with a 2.33:1 male-to-female ratio, and 60% NMIBC versus 40% MIBC. Subtypes identified were IHC luminal (55%), IHC basal (19%), IHC dual (22%), and IHC dual (4%). IHC luminal subtype demonstrated the highest overall survival rate (80%), followed by IHC dual (72.72%), IHC basal (63.15%), and IHC dual with the lowest survival (25%). KRT5-positive tumors exhibited a crude hazard ratio (HR) of 1.98 in univariate analysis, lacking statistical significance. Conversely, GATA3-positive tumors were significantly associated with lower risk in both univariate (Crude HR=0.36, P=0.01) and multivariate analysis (P=0.01). In addition, lymphovascular invasion significantly increased risk in both univariate and multivariate analyses (adjusted HR=5.26, P<0.01). In conclusion, our study advocates for the early stratification of UC into IHC-based subtypes, facilitated by a panel of 4 markers, offering valuable insights into molecular characteristics, particularly in resource-constrained settings, and aiding clinical stratification.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhi Chen Liu, Wen Ming Tang, Li Jun Zhou, Yong Hui Zhang, Jia Hao Zhang, Liang Yan, Jun Li, Hai Hang Feng, Xiao Ming Li, Chun Li
{"title":"The Expression and Clinical Features of 8 Immunohistochemistry Markers in Adrenal Cortical Adenomas and Pheochromocytomas.","authors":"Zhi Chen Liu, Wen Ming Tang, Li Jun Zhou, Yong Hui Zhang, Jia Hao Zhang, Liang Yan, Jun Li, Hai Hang Feng, Xiao Ming Li, Chun Li","doi":"10.1097/PAI.0000000000001271","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001271","url":null,"abstract":"<p><p>This study explores the potential relationship between 8 immunohistochemistry markers and 4 adrenal diseases-cushing syndrome, primary hyperaldosteronism, nonfunctioning adrenal adenoma, and hypercatecholamine-based on symptoms and laboratory findings. Understanding these associations can provide valuable insights into the diagnosis and management of adrenal tumors. We retrospectively analyzed cases of patients treated in the urology department of our hospital from April 2017 to May 2022, focusing on pathologic results of specimens that had undergone immunohistochemical staining following laparoscopic adrenalectomy. The statistical analysis was performed using the χ2 test with SPSS 25.0 software. A total of 124 cases were collected, including 71 men and 53 women. Among them, 21 cases were diagnosed with cushing syndrome, 49 with primary hyperaldosteronism, and 40 with nonfunctioning adrenal adenoma, all reported as adrenal cortical adenomas. In addition, 14 cases were diagnosed with hypercatecholamine, reported as pheochromocytoma. The expression of Melan-A, inhibin α, and vimentin was significantly higher in adrenal cortical adenomas compared with pheochromocytoma (P<0.05), while CgA and S100 were more noticeable in pheochromocytoma (P<0.05). However, there was no significant difference in the expression of Syn, β-catenin, and CK between these 2 groups. Further comparisons revealed no significant differences among cushing syndrome, primary hyperaldosteronism, nonfunctioning adrenal adenoma, and hypercatecholamine concerning these 8 markers. The same applied when comparing nonfunctioning adrenal adenoma and functional adrenal adenoma (cushing syndrome and primary hyperaldosteronism). Our findings suggest that the combination of Melan-A, inhibin α, vimentin, CgA, and S100 may be useful in distinguishing between adrenal cortical adenoma and pheochromocytoma. However, these markers are not reliable for distinguishing among cushing syndrome, primary hyperaldosteronism, hypercatecholamine, and nonfunctioning adrenal adenoma.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iusta Caminha, Juliana Cordeiro, Francisco Martins Neto, Marclesson Alves, Paulo G Silva, Guilherme Sousa, Fabio Tavora, Luciano Pamplona
{"title":"Immune Profiling of Incidental NSCLC Patients: Comparison Between Tumor Sections and TMA Cores.","authors":"Iusta Caminha, Juliana Cordeiro, Francisco Martins Neto, Marclesson Alves, Paulo G Silva, Guilherme Sousa, Fabio Tavora, Luciano Pamplona","doi":"10.1097/PAI.0000000000001266","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001266","url":null,"abstract":"<p><p>In the context of nonsmall cell lung cancer (NSCLC), the immune evasion strategy used by tumor cells involves the expression of immune checkpoint proteins, such as PD-L1, which suppress antitumor T-cell responses. The use of immune checkpoint inhibitors (ICIs) has significantly improved overall survival, overall response rate, and progression-free survival in NSCLC patients. This study aimed to evaluate the concordance of PD-L1 expression in NSCLC patients using tissue microarrays (TMA) as proxies for small biopsies. The degree of concordance among tissue cores and between the cores and the whole slide was reported. Furthermore, the presence of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) was analyzed to investigate the correlation between PD-L1 expression and immune cell infiltration. The study included 13 paraffin-embedded tissue samples from patients incidentally diagnosed with lung cancer during COVID imaging studies. Tissue microarrays were constructed using a manual tissue arrayer, and 4 cores of 2 mm diameter of representative areas were selected from the hematoxylin-eosin-stained sections from lung tumor specimens. Immunohistochemical analyses were performed to assess PD-L1 positivity, tumor macrophage infiltrate, and T-cell infiltrate. The density of CD8+ T cells was evaluated as the overall percentage of the area within the borders of the tumors covered by positive immune cells. Results demonstrated that PD-L1 expression showed a high degree of concordance between TMA cores and whole tumor sections, suggesting that small samples could reliably represent whole tumor PD-L1 status. However, the densities of CD8+ T cells and CD68+ macrophages varied significantly. TMA cores typically underrepresented the density of these immune cells compared with whole sections, particularly for CD68+ macrophages, which exhibited lower densities in TMAs, used as proxies for small biopsies. This study contributes to the understanding of how the heterogeneity of PD-L1 expression and immune cell distribution can influence the detection and scoring of these parameters, highlighting the importance of comprehensive immune profiling in guiding personalized cancer immunotherapy.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ki Rim Lee, Soon Auck Hong, Mineui Hong, Joo Young Kim
{"title":"Expression of Hippo Pathway Molecules in Distal Bile Duct Cancer.","authors":"Ki Rim Lee, Soon Auck Hong, Mineui Hong, Joo Young Kim","doi":"10.1097/PAI.0000000000001268","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001268","url":null,"abstract":"<p><p>The Hippo pathway is a tumor-suppressive pathway. Hippo pathway dysregulation correlates with cancer progression, metastasis, and a poor prognosis. Large tumor suppressor homolog 1/2 (LATS1/2), Yes-associated protein (YAP), and TEA domain-containing sequence-specific transcription factor 4 (TEAD4) are primary Hippo pathway components. We evaluated LATS1/2, YAP, and TEAD4 expression and their correlation with clinicopathological behavior and prognostic significance in 67 distal bile duct cancer (DBDC) cases. LATS1/2 expression was observed in 20 (29.9%) DBDC cases and correlated significantly with low pT classification, absence of lymphovascular invasion, and low American Joint Committee on Cancer (AJCC) stage. High YAP expression was identified in 35 (52.2%) cases and correlated with high pT classification, AJCC stage, and TEAD4 expression. High TEAD4 expression was observed in 13 (19.4%) cases and correlated significantly with lymph node metastasis, involved resection margins, and high AJCC stage. Overall survival was significantly better in patients with DBDC with than in those without LATS1/2 expression (P < 0.001), and significantly worse in patients with high than in those with low YAP and TEAD4 expression (P = 0.014, 0.037, respectively). The overall survival of patients with combined LATS1/2+YAP or TEAD4low expression was significantly better than that of other groups [hazard ratio (HR) 5.809; 95% CI, 1.770-19.065; P = 0.001]. This combination was an independent good prognostic factor (HR 4.399; 95% CI, 1.313-14.743; P = 0.016) in patients with DBDC. LATS1/2, YAP, and TEAD4 expression correlates with DBDC clinicopathological behavior and may be useful prognostic markers in patients with DBDC.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Value of Routine Reflex In Situ Hybridization Testing in Low-grade Tubule-forming Invasive Breast Cancers With Equivocal HER2 Immunohistochemistry: A Reappraisal of the ASCO/CAP Guidelines.","authors":"Seyed Reza Taha, Fouad Boulos","doi":"10.1097/PAI.0000000000001269","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001269","url":null,"abstract":"<p><p>Guidelines from the American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) recommend an equivocal score (2+) and reflex in situ hybridization (ISH) testing for invasive breast cancer (IBC) with moderate to strong lateral or basolateral staining by HER2 immunohistochemistry (IHC). While this recommendation mainly addresses aggressive tumor types such as micropapillary carcinoma, it is applied to low-grade, tubule-forming IBCs unlikely to show HER2 amplification. A total of 62 cases of IBC with equivocal HER2 IHC, low histologic grade (1/3), and tubule formation scores of 1 or 2 according to Nottingham criteria were retrospectively identified from 2020 to 2023 to determine the frequency of HER2 amplification using fluorescent ISH (FISH). Following slide review, 3 cases were reclassified as grade 2, leaving 59 cases for analysis. Demographic and clinicopathological data were collected from medical records and analyzed. A total of 98.3% of cases were not amplified by HER2 FISH, with only 1 case showing amplification. All cases were ER positive. Oncotype DX scores, available for select cases, showed low recurrence scores (below 25). The single HER2-amplified case contained a ductal carcinoma in situ component with HER2 3+ staining, potentially leading to a false positive result. In conclusion, HER2 amplification is rare in low-grade, tubule-forming IBCs. These results suggest reconsidering current guidelines to reduce unnecessary FISH testing, potentially improving cost-effectiveness and clinical efficiency without compromising diagnostic accuracy.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD140b (PDGFRB) Expression in Atypical Fibroxanthoma/Pleomorphic Dermal Sarcoma and its Cutaneous Neoplastic Mimics.","authors":"Tayler Gant, Wonwoo Shon","doi":"10.1097/PAI.0000000000001267","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001267","url":null,"abstract":"<p><p>Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are closely related tumors, believed to represent a continuum of the same neoplastic process, sharing numerous clinical features as well as morphologic, immunohistochemical, and genetic characteristics. Recently, whole-exome sequencing analysis revealed high-level PDGFRA/B gene expression and suggested PDGFRB immunohistochemistry as a \"lineage specific\" marker for PDS. To evaluate the potential diagnostic utility of PDGFRB status, we examined CD140b (PDGFRB) protein expression in a well-characterized cohort of AFX, PDS, and morphologic mimics. Formalin-fixed, paraffin-embedded sections from 18 AFX, 8 PDS, 26 squamous cell carcinomas (9 sarcomatoid, 11 poorly differentiated, and 6 moderately differentiated), 39 melanomas (including 10 desmoplastic and 6 spindle cell), 7 cutaneous leiomyosarcomas, and 2 cutaneous pleomorphic rhabdomyosarcomas were retrieved. CD140b expression was scored by extent (0 to 3+) and intensity (0 to 3) of staining. All AFX and PDS were diffusely positive (26/26). CD140b showed a variable extent of staining in 5/26 squamous cell carcinoma (5/9 sarcomatoid and 0/17 poorly/moderately differentiated SCC) and 16 of 39 melanomas (10/10 desmoplastic, 1/6 spindle cell, and 5/22 nondesmoplastic/spindled). Partial positivity was observed in 2/7 cutaneous leiomyosarcoma, while diffuse staining was present in both (2/2) cases of cutaneous pleomorphic rhabdomyosarcoma. In summary, CD140b is a sensitive but imperfectly specific marker for AFX and PDS. Several targeted drugs have shown efficacy in PDGFR-expressing tumors, and our findings further delineate therapeutic strategies for a selected group of poorly differentiated cutaneous neoplasms.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehrjoo Amraie, Mohammadhossein Khorraminejad-Shirazi, Ali Nabavizadeh, Maral Mokhtari
{"title":"Evaluation of Diagnostic Accuracy of Immunohistochemical Markers of SATB2 and Villin in Differential Diagnosis of Ovarian and Gastrointestinal Mucinous Carcinoma.","authors":"Mehrjoo Amraie, Mohammadhossein Khorraminejad-Shirazi, Ali Nabavizadeh, Maral Mokhtari","doi":"10.1097/PAI.0000000000001265","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001265","url":null,"abstract":"<p><p>Determining the origin of mucinous adenocarcinomas can be challenging due to overlapping histologic and immunohistochemical features. This study evaluates the utility of SATB2 and villin immunohistochemical markers for defining mucinous adenocarcinomas' origin. We retrospectively analyzed 71 patients with mucinous adenocarcinomas-31 lower gastrointestinal (GI), 28 ovarian, and 12 cases of pseudomyxoma peritonei. Immunohistochemistry for SATB2 and villin was performed on ovarian and GI tumor samples. Sensitivity, specificity, and positive and negative predictive values were calculated to assess diagnostic performance.For identifying GI origin, SATB2 showed 87.1% sensitivity and 100% specificity, while villin exhibited 93.5% sensitivity but only 21.4% specificity. Dual SATB2/villin positivity demonstrated 80.6% sensitivity and 100% specificity for GI origin. For ovarian origin, dual SATB2/villin negativity provided 100% specificity. Logistic regression analysis on the adenocarcinoma cases showed 93.2% accuracy rate of dual staining with SATB2 and villin for predicting GI versus ovarian origin. SATB2 exhibits high specificity for GI mucinous adenocarcinomas, and villin is highly sensitive. Combining SATB2 and villin optimizes diagnostic performance for differentiating the primary origin site of mucinous adenocarcinomas and determining pseudomyxoma peritonei origin. Moreover, the presence of signet ring morphology prompted reconsideration of possible GI origin among our cases. A multimarker immunohistochemical panel, including SATB2 and villin can enhance the diagnostic accuracy of challenging mucinous adenocarcinoma cases.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of Proteinase-activated Receptor 2 (PAR2) as a Correlate of Concern in Triple-negative Breast Cancer (TNBC).","authors":"Gargi Kapatia, Subhpreet Kaur, Sandeep Kumar, Ishita Laroiya, Gurpreet Singh, Maryada Sharma, Amanjit Bal, Manni Luthra-Guptasarma","doi":"10.1097/PAI.0000000000001025","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001025","url":null,"abstract":"<p><strong>Purpose: </strong>Triple-negative breast cancer (TNBC), a highly aggressive cancer with poor outcome and lacking specific diagnostic, prognostic, or targeted therapeutic strategies, constitutes roughly 20% of all breast cancer cases. TNBC cells lack receptors for estrogen, progesterone, and human epidermal growth factor. The effort continues to find a suitable correlate that could serve as a TNBC biomarker, or as therapeutic target, or both.</p><p><strong>Materials and methods: </strong>A retrospective study was performed with 88 TNBC and 74 non-TNBC patients who had undergone mastectomy/lumpectomy with axillary clearance for carcinoma breast. Immunohistochemical staining was carried out for levels of proteinase-activated receptor 2 (PAR2), encoded by F2RL1 gene, and staining scores were calculated, based on intensity and percentage positivity.</p><p><strong>Results: </strong>PAR2 levels were markedly upregulated in TNBC patients, compared with patients with other breast cancer subtypes. Amongst different non-TNBC subtypes, higher expression was noted in luminal B (88.8%) and HER2+ (100%), compared with luminal A (52.5%). PAR2 levels were significantly high in TNBC patients with age more than 40 years than corresponding patients of non-TNBC group (P=0.0017). Furthermore, there was a statistically significant increase in levels of PAR2 expression in lymph node negative (P=0.0096) and early stage (P=0.005) of TNBC versus non-TNBC patients. PAR2 staining of ductal carcinoma in situ and invasive ductal carcinoma revealed lower expression in invasive component.</p><p><strong>Conclusions: </strong>Our data suggest that PAR2 levels constitute a correlate of concern for TNBC, tying in with a recent report that higher levels of F2RL1 gene expression correlate with poorer disease-free, as well as overall survival in TNBCs.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"446-452"},"PeriodicalIF":1.6,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40578348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}