Applied Immunohistochemistry & Molecular Morphology最新文献

Aims: To investigate the staining patterns of CD10 in hepatocellular carcinoma (HCC), focal nodular hyperplasia (FNH), and intrahepatic cholangiocarcinoma (ICC).

Methods: The expression pattern of CD10 was analyzed using immunohistochemistry in HCC cases. Focal nodular hyperplasia (FNH) and intrahepatic cholangiocarcinoma (ICC) cases were also examined. CD10 staining pattern in relationship with histologic subtypes and growth patterns of HCC was also analyzed.

Results: CD10 expression was observed in 61% (64/105) of HCC cases, 100% (12/12) of FNH cases, and 31.6% (6/19) of ICC cases. Different expression patterns were noted, including cell membrane (13/64; 20.3%), luminal (9/64; 14.0%), cytoplasmic puncta (15/64; 23.4%), and canalicular (27/64; 42.3%) patterns of CD10 expression in HCC. Interestingly, CD10 membranous expression was found to be associated with steatosis changes. The observed pattern rates of CD10-positive ICC cases were 16.6% (1/6) for cell membrane, 50% (3/6) for cytoplasmic, and 33.3% (2/6) for luminal patterns; with 2 samples having a 1+ score (33.3%), 1 having a 2+ score (16.7%), and 3 having a 3+ score (50%).

Conclusions: Different CD10 expression patterns were observed in HCC, FNH, and ICC. A canalicular CD10 expression pattern does not distinguish between benign and malignant lesions in the HCC, but reduced CD10 expression or no canalicular pattern suggests that a tumor is more likely to be HCC. Contrary to previous understanding, we found that CD10 is also expressed in ICC cases.

Tissue-based biomarkers that identify women with increased breast cancer risk are needed for cancer prevention. Enhancer of zeste 2 (EZH2) and fatty acid synthase (FASN) are associated with breast cancer aggressiveness, but their expression in normal breast tissues and association with breast cancer risk factors are unclear. Further, there is a need to characterize healthy breast tissue cohorts for unbiased biomarker evaluation. In this study, we employed the Susan G. Komen healthy volunteer tissue bank to evaluate EZH2 and FASN expression and their relationship to breast cancer risk factors. Normal breast core biopsies from 40 healthy donors with low or high Gail scores (<11 or >20, respectively) and normal or obese body mass index (BMI, <25 kg/m 2 or >30 kg/m 2 , respectively) were stained for H&E, EZH2, and FASN and scored independently and blindly using the Allred method. We analyzed the associations between EZH2 and FASN with Gail score, BMI, menopausal status, hormone replacement therapy (HRT), and family history of breast cancer. None of the donors had BRCA1/2 mutations or developed breast cancer after 5 to 9 years. We found that premenopausal women had significantly higher expression of FASN and that EZH2 was higher with increasing Gail risk scores, compared with postmenopausal women. In postmenopausal women, increased EZH2 expression was associated with >5 years of HRT compared with <1 year or no HRT. No associations were found with BMI. This study provides validation of a healthy breast tissue cohort and initial characterization of EZH2 and FASN and their associations with breast cancer risk factors.

Abstract: Cytokeratin 7 (CK7) is a marker of epithelial differentiation and is positive in >90% of breast carcinomas. In the right clinical setting, coexpression of CK7 and GATA3 is considered as strong evidence of breast origin, which can be further confirmed by positive expression of estrogen and progesterone receptors. Pathologists use CK7 in the breast to confirm epithelial differentiation and highlight foci of invasion, and outside the breast it is often used as a marker to support breast origin of metastatic tumors. Few studies have reported loss of CK7 in invasive breast carcinoma, however, association of CK7 loss with any histopathologic subtype has not been well documented in the literature. We stained a series of solid papillary carcinoma of the breast (SPC) and associated invasive ductal carcinoma (IDC) with CK7 to document that CK7 loss can occur in both SPC and associated IDC. Archived breast tumor tissue specimens with a diagnosis of SPC with IDC were identified from our Department of Pathology database from January 2019 to January 2023. Blocks with tumors were initially evaluated on Hematoxylin and Eosin (H&E) slides, and subsequently with CK7, synaptophysin, and chromogranin immunostains. The results of these immunohistochemical markers were tabulated in an Excel sheet. Expression of CK7 was entered as negative, marked loss of CK7 (weak positive staining in <1% of tumor), and positive (diffuse expression >1% to 100% of tumor cells). Out of 26 tumors of SPC, 15 showed negative to a marked loss of expression for CK7 in both in-situ and invasive components (57.7%), while 11 were diffusely positive (42.3%). Neuroendocrine differentiation was present in 57.7% of tumors of which 60% were CK7 negative. However, there was no significant association between neuroendocrine differentiation in SPC and associated IDC with CK7 loss ( P =1). In addition, histologic parameters, biomarkers expression, Ki-67 expression, and clinical follow-up were studied in detail.

Conclusion: A significant proportion of solid papillary carcinoma of the breast and the associated invasive component can show loss of CK7.

Large/aggressive B-cell lymphomas are diverse both in terms of clinical presentations and treatment response. Diagnostic pathologic evaluation typically begins with a CD20/CD3 immunohistochemical panel. Prebiopsy steroid treatment has been reported to delay diagnosis and subsequent treatment due to altering histomorphology and immunohistochemical staining patterns. This study investigates the impact of prebiopsy steroid use on morphology and immunohistochemical staining patterns in large B cell lymphoma and/or mature B cell lymphomas with high Ki67 expression. Fourteen cases of B cell lymphoma treated with prebiopsy steroids and 13 cases of treatment-naive large B cell lymphoma and/or mature B cell lymphomas with high Ki67 expression were included in this study. Clinicopathological parameters, including type, dose, and route of steroid administration, were documented. Histopathologic slides from both groups were examined to assess morphology and immunohistochemical staining patterns. Morphologically significant effects attributable to steroid administration included significant histiocytic infiltrate and lack of diffuse pattern of infiltration of the lymphoma cells. The CD20 staining pattern, characterized by cytoplasmic/granular distribution and extracellular spillage, showed a statistically significant increase in the steroid group compared with the control group ( P =0.011). This alteration was more prevalent among patients treated with intravenous dexamethasone, high-dose corticosteroids over a short term, and with shorter dosing intervals. Prebiopsy corticosteroid administration induces changes in histomorphology and immunohistochemical staining patterns, particularly affecting CD20, thereby posing diagnostic challenges. The extent of these effects varies depending on the type, route, dosage, and duration of steroid administration.

The histologic differential diagnosis between intracranial hemangioblastoma (HB) and metastatic clear cell renal cell carcinoma may be challenging, especially considering that both tumors exhibit clear cell morphology and can be associated with vHL mutation and/or Von Hippel-Lindau syndrome. As the execution of immunohistochemical analyses is often mandatory, the expression of PAX8 has been traditionally considered a reliable marker of metastatic clear cell renal cell carcinoma, being consistently negative in intracranial HB. However, as in recent years, some cases of PAX8-positive HBs have been reported in the literature; we studied the expression of this antibody on a series of 23 intracranial HB, showing that about 40% of these tumors may express PAX8 and that this immunoreactivity is often focal and weak. We would like to emphasize that the possibility of a PAX8-positive intracranial HB does exist and must be taken into account by neuropathologists to avoid misdiagnoses; in this regard, a broader immunohistochemical panel also including CD10, Inhibin-α, PAX2, S100, and anti-Renal cell carcinoma (RCC) antibody is highly recommended.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm requiring a high index of suspicion, especially on small biopsies. Smooth muscle myosin heavy chain (SMMHC) is a common immunohistochemical (IHC) stain that has been reported to mark normal nodal follicular dendritic cells (FDCs). We hypothesize that SMMHC can be a sensitive marker for FDCS and aim to compare its performance with established markers of FDCS. The archive of a large academic center was searched for cases of FDCS. Clinical features, including age, sex, and site at diagnosis, were reviewed. A hematoxylin and eosin-stained slide was evaluated to assess for morphology and presence of hyaline vascular Castleman disease. The established FDC markers CD21, CD23, fascin, clusterin, and D2-40 were reviewed and compared with SMMHC for all cases. The staining pattern was classified as positive (strong or weak) or negative. Seven unique cases of nodal and extranodal FDCS were collected. SMMHC was positive in most cases (n=5) and performed similarly to established FDC markers, including clusterin, CD21, and CD23 (n=7 each), and fascin and D2-40 (n=4 each). SMMHC was also negative in all 14 examined cases among 5 common differential diagnoses. We demonstrate that the common IHC marker SMMHC has high specificity and similar sensitivity as established FDC markers in nodal and extranodal FDCS, and is useful in the evaluation of common neoplastic mimics.

Histologic grade is a key predictor for pseudomyxoma peritonei (PMP) of appendiceal origin that is used to guide clinical management. However, some tumors demonstrate disease behavior that deviates from their histologic grade. A recent study suggested that TP53, GNAS , and RAS mutation analysis could stratify tumors into distinct molecular groups with different prognosis. We investigated molecular alterations in 114 patients with PMP of appendiceal origin who were uniformly treated with cytoreductive surgery with intraperitoneal chemotherapy (CRS+IPCT). Tumors were separated into 4 groups based on their predominant genomic alteration: RAS -mut, GNAS -mut, TP53 -mut, and triple-negative ( RAS/GNAS/TP53 -wildtype). The results were correlated with World Health Organization (WHO) grade, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS) from the time of CRS+IPCT using multivariate Cox proportional hazard analysis. Fifty percent of TP53 -mut were WHO grade 3 compared with 38% triple-negative, 10% RAS -mut, and 7% GNAS -mut tumors ( P <0.001). The TP53 -mut group exhibited a significantly reduced OS compared with other groups ( P <0.001). No significant OS difference was identified between RAS -mut, GNAS -mut, and triple-negative groups ( P >0.05). In grade 3 PMP, TP53 -mut was significantly associated with reduced OS ( P =0.002). In the multivariate analysis for OS after CRS+IPCT, TP53 -mut [hazard ratio (HR) 3.23, P =0.004] and WHO grade (grade 2 HR 2.73, P =0.03 and grade 3 HR 5.67, P <0.001) were the only independent predictors of survival. Our results suggest that, in addition to tumor grade, TP53 status may help to provide a more patient-centered approach in guiding therapy in PMP.

PRAME is a cancer testis antigen whose expression is limited in normal tissues but is increased in cancers. Although there are studies revealing its oncogenic and immunogenic role, the relationship between PRAME expression and immunity in melanomas is not very clear. We aimed to reveal the relationship between PRAME expression and clinicopathologic parameters, immunologic markers, survival in melanomas. PRAME alteration data in TCGA SKCM data set was obtained from cBioPortal. Analyzes regarding clinicopathologic parameters were performed through cBioPortal and UALCAN, survival-related analyzes were performed through cBioPortal, GEPIA2. The correlation analyzes between PRAME expression and immune cell infiltration, immunity-related genes were performed in TIMER2.0, TISIDB, GEPIA2. PRAME protein-protein interaction network was constructed in STRING. The correlated genes with PRAME were listed in LinkedOmics, gene set enrichment and pathway analyses were performed through LinkInterpreter. In cases with low PRAME expression, there was a higher frequency of metastasis and p53 mutation, a more advanced tumor stage and a lower nodal stage. Strong relationship between PRAME expression and immune cell infiltration. A negative correlation was detected between expression of PRAME and many immunomodulatory genes ( P <0.05). Positively correlated genes with PRAME expression were involved in metabolic pathways; negatively correlated genes were involved in pathways related to cell differentiation, immunologic processes. No significant relationship was found between PRAME expression and survival ( P >0.05). Our findings reveal a strong interaction between PRAME expression and tumorigenicity, the immune system and shed light on further clinical studies including PRAME -targeted studies.

Melanoma antigen gene-A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in a variety of malignancies. However, the expression of MAGE-A2 for clinical values in the pathophysiology of renal cell carcinoma (RCC) is unknown. For the first time, the present study was conducted to examine the expression and prognostic significance of MAGE-A2 expression in clear cell RCC (ccRCC). MAGE-A2 expression was assayed in 162 well-defined ccRCC samples using immunohistochemistry staining on tissue microarrays. The association between MAGE-A2 expression and clinic-pathologic features as well as survival outcomes were then performed. A significant and positive correlation was found between cytoplasmic expression of MAGE-A2 with tumor size ( P =0.008), nucleolar grade ( P =0.001), tumor stage ( P =0.001), microvascular invasion ( P =0.001), invasion to renal pelvis ( P =0.032), renal sinus fat ( P =0.004), and Gerota's fascia ( P =0.028) as well as histologic tumor necrosis ( P <0.0001). Increased expression of MAGE-A2 was observed to be associated with shorter progression-free survival (PFS) compared with patients with low expression of MAGE-A2 ( P =0.032). Multivariate analysis revealed that tumor size and nucleolar grade are independent predictors of the PFS ( P =0.054, P =0.032, respectively). Our results indicated that increased cytoplasmic expression of MAGE-A2 is associated with the malignant degree and progression of ccRCC. This data improved the significance of MAGE-A2 expression and will potentially allow using MAGE-A2 for the prognosis of the disease and immunotherapy in patients with ccRCC.