{"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":"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":"315-320"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","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}
Deniz Bayçelebi, Şemsi Yildiz, Levent Yildiz, İlknur Türkmen
{"title":"STAT6 Can Be Used in the Diagnosis of Hodgkin Lymphoma: There Are Differences in Expression Among Subtypes.","authors":"Deniz Bayçelebi, Şemsi Yildiz, Levent Yildiz, İlknur Türkmen","doi":"10.1097/PAI.0000000000001277","DOIUrl":"10.1097/PAI.0000000000001277","url":null,"abstract":"<p><p>New markers are needed to aid in the diagnosis, typing, and determination of targeted treatment options in Hodgkin lymphoma. STAT6 is one of the most frequently reported mutations in classic Hodgkin tumors and can also be detected immunohistochemically. Our study aimed to investigate the role of the STAT6 (EP325) immunostain, diagnosing Hodgkin lymphoma, its staining frequency, immunolocalization, and its relationship with EBV. Sixty-eight patients representing each Hodgkin lymphoma subtype were included in the study. Two patients had nodular lymphocyte-predominant type Hodgkin, 32 had nodular sclerosis, 14 had mixed type, 10 had lymphocyte-depleted, and 10 had lymphocyte-rich type Hodgkin subtypes. STAT6 (EP325), CD30 (Ber-H2), EBV (CS.1-4) immunohistochemistry, EBER CISH and H&E slides applied to the tumors were examined. STAT6 was positive in 90% (61/68) of all lymphomas. Immunoreactivity with STAT6 was present in all tumors of the nodular sclerosis and lymphocyte-depleted subtypes. A total of 10/14 (71%) of mixed cell subtype tumors and 9/10 (90%) lymphocyte-rich subtype tumors were STAT6 positive. STAT6 staining was not detected in 2 (100%) nodular lymphocyte-predominant subtype. A total of 31% (19/61) of STAT6-positive tumors were also positive for EBV. While STAT6 positivity may be diagnostic of classic Hodgkin's subtypes, STAT6 negativity may be useful for diagnosis of nodular lymphocyte predominant type.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"277-282"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736571","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":"EWSR1::NFATC2 Rearranged Sarcoma : Distinct Clinicopathological Features From a Series of 5 Rare Cases.","authors":"Balamurugan Thirunavukkarasu, Pragya Shukla, Deepam Pushpam, Rachana Meena, Venkatesan Sampath Kumar, Jyoti Pal, Ekta Dhamija, Adarsh Wamanrao Barwad, Asit Ranjan Mridha","doi":"10.1097/PAI.0000000000001274","DOIUrl":"10.1097/PAI.0000000000001274","url":null,"abstract":"<p><p>Ewing sarcoma (ES) is an undifferentiated round cell sarcoma affecting children and young adults. It is characterized by gene fusions involving one of the gene members of FET family ( EWSR1 ) and ETS transcription family members. Recent studies have observed certain undifferentiated round cell sarcomas with EWSR1 -non-ETS fusions, particularly EWSR1::NFATC2 fusion. We identified 5 cases of EWSR1::NFATC2 fusion sarcomas. There was male preponderance and all the patients had a history of trivial trauma. It affected the distal femur and proximal tibia with destructive osteolytic lesions. There was morphologic heterogeneity ranging from round cells in a myxo hyaline stroma to sheets of round-to-spindle cells in a fibrotic stroma. All the cases showed immunopositivity for MIC2, NKX2.2, and NKX3.1, and one showed focal positivity for AE1/AE3 (dot-like) and SATB2. Fluorescence in situ hybridization showed EWSR1 gene rearrangement and amplification (red signals) at 5' end in all the cases classic of EWSR1::NFATC2 sarcoma. Two of the cases showed multiple relapses despite chemotherapy. Though there is morphologic and immunohistochemical overlap with Ewing sarcoma, this entity has been listed separately within the group of undifferentiated small round cell sarcomas.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"295-305"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693034","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":"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":"283-288"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","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}
Nada N Tamem, Shadia H Mabrouk, Zeinab A Shehabeldin, Nivine M A Gado, Manal I Salman, Safaa M M Abd El Khalek
{"title":"Immunohistochemical Study on Programmed Death Ligand 1 (PD-L1) in Breast Carcinoma and Its Correlation With the Clinicopathological Parameters.","authors":"Nada N Tamem, Shadia H Mabrouk, Zeinab A Shehabeldin, Nivine M A Gado, Manal I Salman, Safaa M M Abd El Khalek","doi":"10.1097/PAI.0000000000001278","DOIUrl":"10.1097/PAI.0000000000001278","url":null,"abstract":"<p><p>Breast cancer (BC) is considered to be the second highest cause of cancer-related death in women. Antibodies targeting programmed death ligand 1 (PD-L1) have been approved for treating breast cancer. However, PD-L1 expression and its prognostic role in BC is still the target of several researches in order to maximize its therapeutic role in different clinicopathological settings. This study aimed to evaluate PD-L1 immunohistochemical expression in both tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) in breast carcinoma in cases with and without preoperative neoadjuvant chemotherapeutic treatment and to correlate its association with clinicopathological variables and disease-free survival (DFS). Ninety cases of breast carcinoma mastectomy specimens were collected and stained immunohistochemically for PD-L1. PD-L1 expression was evaluated in TCs and TILs in the 2 settings of cases: (group A) in which the patients did not receive preoperative neoadjuvant chemotherapy (NAC) and (group B) in which the patients received preoperative NAC. The expression of PD-L1 was correlated with clinicopathological parameters. Survival analysis was conducted to correlate disease-free survival (DFS) with PD-L1 expression. In group A, 31.1% of cases showed PD-L1 expression by TCs and 47.5% showed PD-L1 expression by TILs. In group B, 13.8% of cases showed PD-L1 expression by TCs and 41.4% showed PD-L1 expression by TILs. PD-L1 expression in both TCs and TILs is significantly associated with poor prognostic factors in breast cancer. In cases with residual cancer after neoadjuvant chemotherapy, PD-L1 expression remains prominent in TILs, suggesting ongoing immune resistance.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"321-329"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736570","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}
Uiree Jo, Min Jeong Song, Ji-Seon Jeong, Halim Song, Joon Seon Song
{"title":"Distinct levels of DDIT3 Amplification in Dedifferentiated Liposarcoma Developing After DDIT3 Rearrangement in Myxoid Liposarcoma.","authors":"Uiree Jo, Min Jeong Song, Ji-Seon Jeong, Halim Song, Joon Seon Song","doi":"10.1097/PAI.0000000000001275","DOIUrl":"10.1097/PAI.0000000000001275","url":null,"abstract":"<p><p>Dedifferentiated liposarcoma (DDLPS) is a high-grade tumor characterized by its diverse histomorphology and development from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS). The variable morphology of DDLPS, particularly its similarity to myxoid LPS, necessitates a reliable diagnostic tool for accurate diagnosis. While DDIT3 rearrangement is a known characteristic of myxoid LPS, its amplification in DDLPS has not been extensively studied. To investigate this, we evaluated DDIT3 amplification in 29 DDLPS cases from Asan Medical Center over a 7-year period using fluorescence in situ hybridization, with immunohistochemistry for MDM2 and CDK4 performed for diagnostic confirmation. Our findings revealed DDIT3 amplification in 89.7% (26/29) of DDLPS cases, with a mean copy number of 7.4. While no significant differences in clinical characteristics or outcomes were observed between patients with and without DDIT3 amplification, patients with <4 copies of DDIT3 amplification showed a tendency toward shorter disease-free survival. These findings demonstrate the prevalence of DDIT3 amplification in DDLPS, suggesting its potential diagnostic and therapeutic significance. Additional research is necessary to fully understand the prognostic implications of DDIT3 amplification levels in DDLPS and its potential application in targeted therapies.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"289-294"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763022","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":"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 TEAD4 low 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":"330-338"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","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}
Dilara Akbulut, Seher Yuksel, Ekin Kircali, Burak Yasin Aktas, Secil Demirkol Canli, Beyza Doganay Erdogan, Gulsah Kaygusuz, Arzu Ayhan Saglam, A Figen Soylemezoglu, Aysegul Uner, Muhit Ozcan, Alev Turker, Isinsu Kuzu
{"title":"Immune Checkpoint Molecule Expression, 9p24.1 Gene Alterations, and Tumor Microenvironment of Primary Central Nervous System Lymphomas and Their Clinical Relevance.","authors":"Dilara Akbulut, Seher Yuksel, Ekin Kircali, Burak Yasin Aktas, Secil Demirkol Canli, Beyza Doganay Erdogan, Gulsah Kaygusuz, Arzu Ayhan Saglam, A Figen Soylemezoglu, Aysegul Uner, Muhit Ozcan, Alev Turker, Isinsu Kuzu","doi":"10.1097/PAI.0000000000001273","DOIUrl":"10.1097/PAI.0000000000001273","url":null,"abstract":"<p><p>Primary central nervous system large B-cell lymphoma (PCNS-LBCL) is a rare, aggressive lymphoma that affects immune-privileged sites. Immune checkpoint molecules have been implicated in its aggressive biology, and promising results have emerged from immune checkpoint inhibitor therapy in relapsed/refractory cases. This study evaluates the tumor microenvironment (TME), immune checkpoint molecule expression, and the relationship with 9p24.1 gene region alterations in a large cohort of PCNS-LBCL, with detailed quantitative analyses. Tissue microarrays were constructed with 57 PCNS-LBCL cases and 45 systemic non-germinal center diffuse large B-cell lymphoma (DLBCL) controls. Immunostaining for CD3, CD8, CD68, CD163, PD-1, PD-L1, PD-L2, EBER in situ hybridization (ISH), and FISH for PD-L1/PD-L2 copy number alterations and translocations were performed. Digital image analysis was used for quantitative evaluations, which were compared with clinical and pathologic parameters. PCNS-LBCL showed significantly lower T-cell and histiocyte presence in the TME compared with nodal DLBCL ( P <0.001), independent of preoperative steroid therapy. Cytotoxic T-cell ratio was higher in PCNS-LBCL ( P <0.001). PD-1, PD-L1, and PD-L2 expressions in the TME of PCNS-LBCL were 89%, 96%, and 90%, respectively, and were positively correlated with TME density. Tumor cell expressions of PD-L1 and PD-L2 were 31% and 34%, respectively. FISH alterations in the 9p24.1 region were infrequent and did not consistently correlate with protein expression in either PCNS-LBCL or DLBCL. Higher CD8+ T-cell and CD68+ histiocyte counts were associated with better survival in PCNS-LBCL. Lower TME density and high expression of PD-1/PD-L1/PD-L2 in PCNS-LBCL reflect the unique CNS microanatomy and may contribute to poorer prognosis. These findings support the potential benefit of immune checkpoint inhibitors in treating PCNS-LBCL, aligning with ongoing clinical trials and current literature.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"306-314"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532649","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}
Jingwei Ma, Meng Zhu, Ning Zhang, Ningbo Huang, Xianyao Meng
{"title":"Comparison of Gastric Signet Ring Cell Carcinoma and Adenocarcinoma From Clinicopathologic Characteristics and Protein Expressions.","authors":"Jingwei Ma, Meng Zhu, Ning Zhang, Ningbo Huang, Xianyao Meng","doi":"10.1097/PAI.0000000000001276","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001276","url":null,"abstract":"<p><p>Signet ring cell carcinoma (SRCC) and adenocarcinoma (ADC) exhibit distinct characteristics, yet a comprehensive comparison is lacking. In this retrospective study from 2020 to 2024, we analyzed 568 gastric cancer cases, including 216 SRCC and 352 ADC. In SRCC, MMR deficiencies were 3.2% for MLH1, 2.3% for PMS2, 0.5% for MSH2, with PMS2 deficiencies more prevalent in old patients and only one MSH2 deletions observed in cardia-involved cases. E-cadherin loss was 13.5%, predominantly in males and cases with nerve invasion, while Claudin18.2 positivity was 49.2%, particularly in early-stage patients. In ADC, MMR deficiencies were 8.5% for MLH1, 6.5% for PMS2, 0.3% for MSH6 and MSH2, with MLH1 and PMS2 deficiencies more common in females, old patients, and antrum-involved cases, and MSH2 deletions associated with larger tumors. E-cadherin loss was 5%, primarily in poorly differentiated and diffuse types, and Claudin18.2 positivity was 50.9%, especially in lymphatic metastasis patients. SRCC was more common in females and younger individuals, peaking 10 years earlier than ADC, which was significantly more prevalent in males. Both localized predominantly in the antrum. SRCC exhibited mucosa and serosa infiltration along with higher local metastasis, while ADC showed gradually increasing infiltration depth. MLH1 and PMS2 deficiencies were more common in ADC, while E-cadherin loss predominantly in SRCC. AB-PAS expression was higher in SRCC. Female and elderly were risk factors for MMR deficiencies in ADC, while female protected against E-cadherin loss in SRCC. These results highlight the need for tailored therapeutic approaches based on distinct molecular and clinical features.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796557","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":"Investigating Biomarkers in Primary Tumors and Lymph Node Metastases in Tongue Squamous Cell Carcinoma: An Immunohistochemical Perspective.","authors":"Shahroo Etemad-Moghadam, Mojgan Alaeddini","doi":"10.1097/PAI.0000000000001280","DOIUrl":"10.1097/PAI.0000000000001280","url":null,"abstract":"<p><p>This study aimed to gain insight into cancer progression and the metastatic process by analyzing protein expression patterns in primary, metastatic, and nonmetastatic tongue squamous cell carcinoma (TSCC), with a focus on understanding biomarker changes between primary tumors and lymph node metastases. A total of 60 TSCC biopsy samples, 20 primary metastatic, 20 lymph node metastatic, and 20 nonmetastatic, were immunohistochemically stained to analyze MCM2, CD44, and E-cadherin expression. Expression levels were assessed through immunoreactivity scores, and differences across groups were evaluated using generalized estimating equations (GEE). No significant differences in biomarker expression were observed between primary tumors and their lymph node metastases. However, significant variations were identified in MCM2 and E-cadherin expression across the groups. MCM2 expression was notably lower in lymph node metastases compared with nonmetastatic TSCC ( P = 0.025), and E-cadherin expression was reduced in primary tumors relative to nonmetastatic samples ( P = 0.028). CD44 expression did not show significant variation across the different groups. The results align with the classic model of TSCC metastasis, suggesting biomarker stability between primary and metastatic sites. However, variations in MCM2 and E-cadherin expression between specific groups highlight their potential roles in TSCC progression. Further investigation into additional markers and pathways could offer a more comprehensive understanding of TSCC metastasis and contribute to more precise therapeutic approaches.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777592","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}