AJUBA is multifunctional scaffold protein which belongs to Zyxin family of proteins. It is known to have dual role in cancer as a tumor promoter and tumor suppressor. AJUBA has a key role in systemic malignancies like esophageal squamous cell carcinoma, colorectal cancer, cervical, breast, prostate cancer, etc. But there is very sparse literature available regarding its expression profile in oral squamous cell carcinoma (OSCC) and moreover its expression has not been observed in normal oral mucosa (NOM). Thus, the aim of this research is to explore the expression profile of AJUBA by immunohistochemical method in NOM and OSCC. Furthermore, we also evaluated the association of AJUBA expression with clinicopathologic parameters. A total of 84 samples of formalin fixed paraffin embedded tissue blocks comprising of 42 cases each of NOM and OSCC were subjected to detect immunoexpression of AJUBA. We found enhanced intense immune-expression of AJUBA in OSCC cases than compared with NOM and found to be statistically significant. The parameters specific to histologic tumor grade and inflammatory response in OSCC also found to have statistically significant with AJUBA expression. Our study is first of its kind to reveal AJUBA expression in basal and suprabasal layer of NOM suggestive of its definitive role in differentiation and stratification process. We also observed its intense expression in peripheral cell of tumor islands of OSCC cases, which can suggest its possible role in tumor growth and progression.

Pulmonary sarcomatoid carcinoma (PSC) is characterized by biphasic tumors with epithelial and mesenchymal phenotype. Little is known about the correlation between histologic, immunophenotypic features and the genetic profile of PSC. We analyzed the expression of epithelial-mesenchymal transition–related markers, adenocarcinoma (ADC) and squamous cell carcinoma lineage-specific markers of 205 PSC cases. The alteration of 5 targeted genes was detected by amplification-refractory mutation system-polymerase chain reaction. The intensity of cytokeratin staining was stronger in epithelial carcinoma (EC) than that of the sarcomatoid component (SC) of pleomorphic carcinoma, while vimentin was positive in only 16.3% (17/104) of EC of pleomorphic carcinoma. There is no significant difference between thyroid transcription factor 1 (TTF-1) expression in the SC (46.5%, 33/71) of pleomorphic carcinoma with ADC components and pure PSC (44.2%, 42/95) without p40 expression (P=0.858). Four cases with ALK rearrangement were confirmed to co-express ALK fusion protein in both the SC and EC. The incidence of EGFR/ALK/KRAS mutation was similar between pleomorphic carcinoma with ADC components (40.6%, 26/64) and TTF-1+ pure PSC (38.2%, 13/34) (P=0.583). However, higher proportions of TTF-1+/p40− PSC patients (44.8%, 39/87) had EGFR/ALK/KRAS mutation than those with TTF-1−/p40− PSC (16.7%, 4/24) (P=0.031). The incidence of EGFR mutation was significantly higher in TTF-1-positive (18.4%, 16/87) than TTF-1-negative (2.7%, 2/74) PSC (P=0.002). No EGFR and ALK abnormality were observed in 24 pleomorphic carcinoma cases with squamous cell carcinoma components or pure PSC with p40 expression. Our study reveals a close correlation between SC and EC components of pleomorphic carcinoma in terms of immunophenotypic and genetic features, which suggests that pleomorphic carcinoma is potentially derived from the sarcomatoid change of EC cells undergoing epithelial-mesenchymal transition.

The human papillomavirus (HPV) status of squamous cell carcinomas (SCCs) of the head and neck is relevant for therapy planning, staging, and follow-up. Immunohistochemistry (IHC) for p16 is a surrogate marker of HPV status in oropharyngeal SCC, but not at other head and neck sites. We tested if the cobas HPV test was feasible and superior to p16-IHC on fine-needle aspiration (FNA) supernatants and frozen section (FS) scrapings of suspected SCC. A 500 μL aliquots of postcentrifugation supernatant CytoRich Red media of FNA cellblock specimens and scrapings of FS suspended in SurePath media vials were tested with the cobas HPV test and compared with p16-IHC and/or HPV in situ hybridization (ISH) performed on cellblock and/or resections. Twenty-nine (n=29) FNAs were tested for a cobas HPV test, p16, and/or HPV-ISH. The mean collection to testing time was 6.3 days (range: 0 to 24 d). Cobas yielded valid results in all cases; p16-IHC could not be interpreted in 4 (13%) cellblocks; correlation was performed on subsequent resections. Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FNA samples was 0.9, perfect agreement, sensitivity 100%, specificity 92.3%, positive predictive value 94.1%, negative predictive value 100%. Thirty-four (n=34) scrapings from FS were tested for cobas, p16, and/or HPV-ISH. The mean collection to testing time was 10.4 days (range: 1 to 28 d). Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FS scrapings was 1, perfect agreement. Sensitivity, specificity, positive predictive value, and negative predictive value was 100%. Cobas genotype was HPV-16 in 87%, HPV-18 in 3%, and HPV-other in 10%. Cobas HPV test in FNA supernatant and FS scrapings outperformed or was equivalent to p16-IHC and provided genotyping information.

Ki-67 is a nuclear protein serendipitously discovered by monoclonal antibody selection in the early 1980s. While it has been applied for decades in the context of breast cancer as a putative prognostic and, more recently, predictive, biomarker, even after all this time there is incomplete agreement as to the validity of the immunohistochemical assays employed for Ki-67 assessment, given possible effects of the disparate methodologies employed and possible confounding preanalytical, analytical, and interpretive variables. In this brief review, the history of Ki-67 and the problems, particularly with the analytical and interpretive variables, are highlighted through a selective review of the published literature. The contributions of the International Ki-67 Breast Cancer Working Group are highlighted, and in particular, the recommendations made by this group are reviewed. The potential of Ki-67 as a biomarker for breast cancer has not yet been fully realized, but an understanding of the power as well as the limitations of the methods of Ki-67 assessment are important if this biomarker can realize its potential.

Pan-TRK antibodies have been used to detect gene fusions in diverse types of tumors. Several tyrosine receptor kinases (TRK) inhibitors have recently been developed and have shown good response rates in neoplasms with NTRK; therefore, identifying these fusions is an essential tool in assessing treatment options for certain oncological diseases. Various algorithms have been designed to diagnose and detect NTRK fusions to optimize time and resources. This study explores the use of immunohistochemistry (IHC) as a screening method for NTRK fusions by comparing next-generation sequencing (NGS) and IHC to evaluate the pan-TRK antibody’s performance as a marker for NTRK rearrangements. The present work studied 164 formalin-fixed paraffin-embedded blocks of different solid tumors. Two pathologists confirmed the diagnosis and selected the correct area to assess with IHC and NGS. Specific cDNAs were generated for the genes involved. NTRK fusions were identified in 4 patients positive for the pan-TRK antibody through NGS. The identified fusions were NTRK1-TMP3, NTRK3-EML4, and NTRK3-ETV6. That shows sensitivity and specificity of 100% and 98%, respectively. NTRK fusions were identified in 4 patients positive for the pan-TRK antibody through NGS. IHC tests (with the pan-TRK antibody) are a sensitive and specific method for identifying the presence of NTRK1-3 fusions.

Lung adenocarcinoma (LUAD) is a malignant tumor with high mortality. At present, the clinicopathologic feature is the main breakthrough to assess the prognosis of LUAD patients. However, in most cases, the results are less than satisfactory. Cox regression analysis was conducted in this study to obtain methylation sites with significant prognostic relevance based on mRNA expression, DNA methylation data, and clinical data of LUAD from The Cancer Genome Atlas Program database. LUAD patients were grouped into 4 subtypes according to different methylation levels using K-means consensus cluster analysis. By survival analysis, patients were grouped into high-methylation and low-methylation groups. Later, 895 differentially expressed genes (DEGs) were obtained. Eight optimal methylation signature genes associated with prognosis were screened by Cox regression analysis, and a risk assessment model was constructed based on these genes. Samples were then classified into high-risk and low-risk groups depending on the risk assessment model, and prognostic, predictive ability was assessed using survival and receiver operating characteristic (ROC) curves. The results showed that this risk model had a great efficacy in predicting the prognosis of patients, and it was, therefore, able to be an independent prognostic factor. At last, the enrichment analysis demonstrated that the signaling pathways, including cell cycle, homologous recombination, P53 signaling pathway, DNA replication, pentose phosphate pathway, and glycolysis gluconeogenesis were remarkably activated in the high-risk group. In general, we construct an 8-gene model based on DNA methylation molecular subtypes by a series of bioinformatics methods, which can provide new insights for predicting the prognosis of patients with LUAD.

The membrane protein angiotensin-converting enzyme-2 (ACE2) has gained notoriety as the receptor for severe acute respiratory syndrome coronavirus 2. Prior evidence has shown ACE2 is expressed within the liver but its function has not been fully discerned. Here, we utilized novel methodology to assess ACE2 expression in pediatric immune-mediated liver disease to better understand its presence in liver diseases and its role during infections such as COVID-19. We stained liver tissue with ACE2-specific immunofluorescent antibodies, analyzed via confocal microscopy. Computational deep learning-based segmentation models identified nuclei and cells, allowing the quantification of mean cellular and cytosolic immunofluorescent. Spatial transcriptomics provided high-throughput gene expression analysis in tissue to determine cellular composition for ACE2 expression. ACE2 plasma expression was quantified via enzyme-linked immunosorbent assay. High ACE2 expression was seen at the apical surface of cholangiocytes, with lower expression within hepatocyte cytosol and nonparenchymal cells (P<0.001). Children with liver disease had higher ACE2 hepatic expression than pediatric control tissue (P<0.001). Adult control tissue had higher expression than pediatric control (P<0.001). Plasma ACE2 was not found to be statistically different between samples. Spatial transcriptomics identified cell composition of ACE2-expressing spots containing antibody-secreting cells. Our results show ACE2 expression throughout the liver, with strongest localization to cholangiocyte membranes. Machine learning can be used to rapidly identify hepatic cellular components for histologic analysis. ACE2 expression in the liver may be increased in pediatric liver disease. Future work is needed to better understand the role of ACE2 in chronic disease and acute infections.

The discovery of almost invariable mouse double minute 2 (MDM2) amplification among atypical lipomatous tumors (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma is incorporated into the contemporary diagnostic workup of fatty lesions. MDM2 amplifications are also found frequently in intimal sarcomas and in low-grade osteogenic sarcoma. At present, fluorescence in situ hybridization (FISH) is the reference test for MDM2 assessment. We are interested in evaluating silver in situ hybridization (SISH) for this purpose. Between October 2016 and May 2020, in 192 consecutive cases requiring MDM2 FISH, SISH was also performed concurrently, including 77 (40.1%) core biopsies and 115 (58.9%) surgical specimens. The mean patient age was 61.0 years. SISH results were available overnight or within 48 hours if repeat testing was required. FISH results were available within 2 to 5 weeks. The cost of SISH was one third of FISH. FISH demonstrated MDM2 amplification in 44 cases (23.6%), was negative in 144 cases (74.4%) and nondiagnostic in 4 decalcified cases (2.0%). SISH showed MDM2 amplification in 33 cases (17.2%), no amplification in 119 cases (62.0%), and indeterminate results because of poor signal in 40 (20.8%) cases. All 33 (100%) SISH-amplified tumors and 113 of 119 (95.0%) nonamplified results were confirmed by FISH. There were no clear differences in the performance of SISH on NCB versus surgical specimens. The overall performance indices of SISH are sensitivity 75%, specificity 78.5%, positive predictive value 100%, and negative predictive value 95.8%. FISH is not required when SISH is clearly amplified. This is clinically useful and improves efficiency. Nonamplified SISH results provide early indications of the likely FISH findings, but there is a 4.2% chance of FISH being positive. At present, the main drawback of SISH is the high rate of nondiagnostic tests. Optimization of SISH signal detection to reduce the proportion of indeterminate results is our current focus.

Loss of caveolin-1 (Cav-1) and upregulation of monocarboxylate transporters (MCTs, especially MCT1 and MCT4) in respectively tumor-associated stromal cells and malignant epithelial cells of invasive carcinoma have been found to play an important role in the metabolic coupling. However, this phenomenon has only been scarcely described in pure ductal carcinoma in situ (DCIS) of the breast. mRNA and protein expression levels of Cav-1, MCT1, and MCT4 in nine pairs of DCIS tissues and matched normal tissues were examined by quantitative real-time polymerase chain reaction, RNAscope in situ hybridization, and immunohistochemistry. Immunohistochemical staining of Cav-1, MCT1, and MCT4 in 79 DCIS samples was also done using tissue microarray. Cav-1 mRNA expression was significantly lower in DCIS tissues than in their corresponding normal tissues. In contrast, MCT1 and MCT4 mRNA expression levels were higher in DCIS tissues than in corresponding normal tissues. Low stromal Cav-1 expression was significantly associated with high nuclear grade. High epithelial MCT4 expression was associated with larger tumor size and human epidermal growth factor 2 positivity. At a mean follow-up of 10 years, patients with high epithelial MCT1/high epithelial MCT4 expression showed shorter disease-free survival than those with other expressions. No significant association was observed between stromal Cav-1 expression and epithelial MCT 1 or MCT4 expression. Changes in Cav-1, MCT1, and MCT4 are associated with carcinogenesis of DCIS. A high epithelial MCT1/high epithelial MCT4 expression might be associated with a more aggressive phenotype.

Nephrogenic adenoma (NA) is an infrequent reactive urothelial lesion. The expression of immunohistochemical renal tubular markers has been reported in NA, although a proximal or distal nephron phenotype has not been established. Special AT-rich sequence-binding protein 2 (SATB2) is a marker of a colorectal origin of adenocarcinomas, occasionally reported in renal samples. We have analyzed SATB2 expression in NA, with correlation with other tubular markers, as well as in the normal kidney. Fifty cases of NA were immunostained with PAX8, SATB2, proximal nephron markers [CD10, renal cell carcinoma (RCC) marker, alpha-methylacyl-CoA racemase (AMACR), and CD15], and distal markers (Ksp cadherin, cytokeratin 7, E-cadherin (E-cad), and cytokeratin 19). Ten normal kidney sections were stained with a double method combining SATB2 plus CD10, RCC marker, AMACR, Ksp cadherin, cytokeratin 7, or E-cad. All NA were immunoreactive for PAX8 and 57% for SATB2. Every case was positive for proximal and distal nephron markers: 100% for cytokeratins 7 and 19, 84.1% E-cad +, 81.6% AMACR +, 68.9% Ksp cadherin +, 63% CD15 +, 53.3% CD10 +, and 28.6 % RCC +. In the normal kidney, SATB2 was detected in the straight part of the proximal tubules and the thin descending loops of Henle. NA shows a multiphenotypic pattern with coexpression of both proximal and distal nephron markers, and constant expression of PAX8, cytokeratins 7 and 19. SATB2 is often positive in NA, which should be kept in mind to avoid a possible misdiagnosis of intestinal adenocarcinoma. SATB2 is a marker of the normal proximal nephron.

Background:  The incidence of oral squamous cell carcinoma (OSCC) of the tongue is increasing in the younger population without traditional risk habits that lead researchers to find other related factors such as diet and viruses, especially human papillomavirus (HPV). It is noteworthy that many OSCCs develop from oral potentially malignant disorders (OPMDs). Correct diagnosis and timely management of OPMDs may help to prevent malignant transformation, and therefore it is worth seeing the involvement of HPV in OPMDs and oral cancers, as the preventive and curative measures in HPV-induced cancer types are different from the conventional types of OPMDs and OSCCs. Therefore, the main objective of this study was to identify a relationship between HPV and p16 in OPMDs and compare it with OSCC. Methods:  This study was conducted on 83 cases of known OSCCs and OPMDs (oral submucous fibrosis, leukoplakia, and oral lichen planus). Assays, such as polymerized chain reaction (PCR) and reverse transcription-PCR, were carried out for HPV and p16. The results were compared with clinical information and with the literature. The results were analyzed using SPSS 16.0 for windows. Results:  P16 expression was mostly seen in males than in female patients. Out of 21 cases of keratosis with dysplasia, 19% expressed p16. Of 26 oral lichen planus patients, 29% showed the p16 gene with immunohistochemistry. Interestingly, a high percentage of OSF cases expressed p16 (48.27%). Minimal expression was observed in OSCC (6.25%). HPV DNA was detected in 2.4% of the total sample. Both p16 and HPV were detected in a single case of OSCC. OPMDs expressed a significant amount of the p16 gene by immunohistochemistry and reverse transcription-PCR technique when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. HPV and p16 are mostly negative in our OSCC sample, exhibiting low prevalence. Conclusions:  OPMDs expressed a significant amount of the p16 gene when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. Although OSF expressed p16, HPV was not detected, suggesting that over-expression could be independent of HPV. OSCC shows low HPV prevalence.

Myeloid cell nuclear differentiation antigen (MNDA) is normally expressed on myelomonocytic cells and a subset of B lymphocytes. It was found to be differentially expressed between nodal marginal zone lymphoma (MZL) and follicular lymphoma (FL). However, MNDA has not been widely used as a diagnostic marker in clinical practice. To validate its utility, we studied the expression of MNDA by immunohistochemistry in 313 cases of small B-cell lymphomas. Our results showed that MNDA was positive in 77.9% of MZL, 21.9% of mantle cell lymphoma, 28.9% of small lymphocytic lymphoma/chronic lymphocytic leukemia, 2.6% of FL, and 25% of lymphoplasmacytic lymphoma. MNDA positivity varied from 68.0% to 84.0% among the 3 MZL subtypes, with extranodal MZL having the highest percentage. There was a statistically significant difference in MNDA expression between MZL and FL, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or lymphoplasmacytic lymphoma. CD43 expression was slightly more frequent in MNDA-negative MZL than in MNDA-positive MZL. Combined use of CD43 and MNDA improved the diagnostic sensitivity for MZL from 77.9% to 87.8%. There was a trend of positive correlation between MNDA and p53 in MZL. In conclusion, MNDA is preferentially expressed in MZL among small B-cell lymphomas and it is a useful marker for the differentiation of MZL and FL.

Medullary Thyroid Carcinoma (MTC) is a tumor of the neuroendocrine system. In recent years, the need to assess the MTC diagnostic-related parameters has emerged with the aim to elucidate the mechanisms involved in this pathology. The objective of this study was to evaluate the role of Matrix Metalloproteinases (MMPs) 2 and 9, their tissue inhibitors of matrix metalloproteinases (TIMPs), S100 protein, and amyloid in the diagnostic of MTC. Thirty-two samples with MTC (72% women) were included in this cross-sectional study and divided by groups: T category 1 (T1)≤20 mm and T category 2 (T2) 20 to 40 mm of tumor size. MMPs 2 and 9, TIMPs 2 and 1, S100 protein, and calcitonin in tissues were obtained by immunohistochemical techniques. The presence of amyloid in tissue sections was detected on Thioflavin T–stained slides under fluorescent microscope. Percentage of positive cells (P) observed for MMP-2 was higher in those samples presenting T2 MTC with respect to those with T1 MTC (P<0.05). Moreover, P-MMP-2 showed a direct correlation with higher T category of MTC (Rho=0.439, P < 0.001), whereas P-MPP-9 was directly correlated with S100 protein and the intensity of calcitonin in tissues (Rho=0.419, P=0.017; Rho=0.422, P=0.016, respectively. Therefore, MMPs were directly correlated with some traditional biomarkers of MTC. In this regard, P-MMP-2 was more expressed in type 2 MTC. Combining the analysis of traditional and other useful biomarkers of MTC as MMPs 2 and 9 could be a useful strategy in the diagnostic of MTC.

The type of fixative used for preserving tumor specimens can significantly impact the performance of the immunohistochemistry and in situ hybridization assays used for assessing human epidermal growth factor receptor 2 (HER2) status. This study reports the prevalence of the use of alternative fixatives other than the guideline-recommended 10% neutral buffered formalin (NBF) during HER2 testing in a real-world setting. The effects of alternative fixatives [20% NBF and 10% unbuffered formalin (UBF) fixatives] on HER2 testing of breast cancer (BC) and gastric cancer (GC) cell lines and tissues are also assessed. Overall, 117,636 tumor samples received at a central laboratory from >8000 clinical trial sites across 60 countries were reviewed to determine the prevalence of alternative fixative usage. To investigate the impact of alternative fixatives, 27 cell lines (21 BC and 6 GC) and 76 tumor tissue samples (50 BC and 26 GC) were fixed in 10% NBF, 20% NBF, or 10% UBF, and evaluated for HER2 status by immunohistochemistry and in situ hybridization. Real-world data showed that 9195 (7.8%) tumor samples were preserved using an alternative fixative. In cell lines, overall percentage agreement, negative percentage agreement, and positive percentage agreement among the 3 fixatives were 100%. In tumor tissues, the agreement among 10% NBF, 20% NBF, and 10% UBF ranged between 94.7% and 96.6% for negative percentage agreement and 90.9% for overall percentage agreement compared with a range of 58.3% to 66.7% for positive percentage agreement. These results suggest that alternative fixatives may have the potential to convert HER2 status in tissues from positive to negative.

To study the extent of heterogeneity of mesothelin overexpression in primary ovarian cancers and their peritoneal and lymph node metastases, a tissue microarray (TMA) was constructed from multiple sites of 220 ovarian cancers and analyzed by immunohistochemistry. One tissue core each was taken from up to 18 different tumor blocks per cancer, resulting in a total of 2460 tissue spots from 423 tumor sites (188 primary cancers, 162 peritoneal carcinosis, and 73 lymph node metastases). Positive mesothelin expression was found in 2041 of the 2342 (87%) arrayed tissue spots and in 372 of the 392 (95%) tumor sites that were interpretable for mesothelin immunohistochemistry. Intratumoral heterogeneity was found in 23% of 168 primary cancer sites interpretable for mesothelin and decreased to 12% in 154 peritoneal carcinosis and to 6% in 71 lymph node metastases (P<0.0001). Heterogeneity between the primary tumor and matched peritoneal carcinosis was found in 16% of 102 cancers with interpretable mesothelin results. In these cancers, the mesothelin status switched from positive in the primary tumor to negative in the peritoneal carcinosis (3 cancers) in or vice versa (2 cancers), or a mixture of positive and negative peritoneal carcinoses was found (11 cancers). No such switch was seen between the mesothelin-interpretable primary tumors and their nodal metastases of 59 cancers, and only 1 mesothelin-positive tumor had a mixture of positive and negative lymph node metastases. In conclusion, mesothelin expression is frequent and highly homogeneous in ovarian cancer.

Ulcerative colitis (UC) and Crohn disease (CD) are cryptogenic inflammatory bowel diseases that are suggestive of aberrant mucin (MUC) expression; however, their relationship remains unclear. Here, we examined aberrant MUC expression in intestinal samples from UC and CD patients in comparison to samples from patients with ischemic colitis and control groups. To study the expression of MUC1, MUC5AC, and MUC6 in different patient groups, we reviewed the slides stained with hematoxylin and eosin and performed immunohistochemistry. The results revealed that MUC1 was expressed more in the UC group and MUC6 in the CD group. No significant changes were observed in MUC expression in the ischemic colitis group. Overall, we demonstrated changes in MUC expression in UC and CD, which can help in the diagnosis and early clinical management of UC and CD.

The aim of this study was to evaluate the immunoexpression of chemokine CXCL12 and its receptor CXCR4 in radicular cysts (RCs), dentigerous cysts (DCs), and odontogenic keratocysts (OKCs), and to correlate the findings with morphologic parameters of RCs (inflammatory infiltrate and cystic epithelium). Twenty RCs, 20 DCs, and 20 OKCs were submitted to immunohistochemistry. The percentages of cytoplasmic (CXCL12 and CXCR4) and nuclear (CXCR4) staining in epithelial and fibrous capsule cells were determined. RCs and DCs exhibited higher epithelial expression of CXCL12 than OKCs (P0.05). Strong positive correlations were found between cytoplasmic and nuclear expression of CXCR4 in the epithelial lining of RCs and DCs and in the fibrous capsule of all groups (P<0.05). The results suggest the participation of CXCL12 and CXCR4 in the pathogenesis of RCs, DCs, and OKCs. These proteins may be particularly relevant for the development of odontogenic cysts with less aggressive biological behavior, irrespective of their nature (inflammatory or developmental). In RCs, the expression of CXCL12 and CXCR4 may not be related to the intensity of the inflammatory infiltrate or the status of cystic epithelium.

Osteoarthritis (OA) is the main joint disease associated with aging. Previous studies have confirmed that both osteopontin (OPN) and αvβ3 integrin are involved in the progression of knee OA. The purpose of this study was to determine the expression of OPN and αvβ3 integrin and chondrocyte senescence levels in OA. Forty-six cartilage tissues from normal and knee OA patients were divided into 4 groups of normal, minor, moderate, and severe lesions based on the Mankin score. Immunohistochemistry and western blotting were used to determine the expression of αvβ3, OPN, and senescent-associated-β-galactosidase (SAβ-gal) in articular cartilage. Then, Spearman’s correlation was used to analyze the correlations between the Mankin scores and αvβ3, OPN and SAβ-gal. Pearson correlation analysis was used to analyze the correlations among αvβ3, OPN, and SAβ-gal. The expression of OPN, αvβ3, and SAβ-gal in articular cartilage was explored. αvβ3, OPN, and SAβ-gal proteins were all elevated in OA cartilage, and the correlation coefficient between the Mankin score and the average optical density value of αvβ3, OPN, SAβ-gal were r=0.60, r=0.75, and r=0.87, respectively, all P<0.001; the correlation between the average optical density value of αvβ3 and OPN was r=0.3191, P<0.05; the correlation between αvβ3 and SAβ-gal was r=0.4955, P<0.001; and the correlation between OPN and SAβ-gal was r=0.7821, P<0.001. The correlations among αvβ3, OPN, and SAβ-gal expression in articular cartilage might be important in OA progression and pathogenesis. Nonetheless, more research is needed to elucidate the exact contribution of αvβ3, OPN, and SAβ-gal to the degenerative process of OA.

BMP-2 and Noggin are expressed in several tissues and participate in cell differentiation and proliferation during odontogenesis and tumor development. We evaluated the immunohistochemical expression of these proteins in ameloblastomas (AMs), odontogenic keratocysts (OKCs), and dentigerous cysts (DCs). The expression in AM (n.20), OKC (n.20), and DC (n.20) was evaluated by the percentage of positive cells and expression intensity, resulting in a total immunostaining score. Analysis of BMP-2 and Noggin revealed positivity in all cases. The Mann-Whitney test showed a statistically significant difference for Noggin between AM and DC and between OKC/DC. The mean DC scores were always higher than those of the other groups, regardless of the assessment method. Individual analysis of each lesion showed a positive and significant correlation between the percentage of cells positive for BMP-2 and Noggin in DC. We demonstrated the presence of BMP-2 and Noggin in AMs/OKCs/DCs. Marked expression of BMP-2 was observed in OKCs and AMs. There was also a positive correlation between BMP-2 and Noggin in DCs, suggesting a greater role of these markers in the bone formation and remodeling process since DCs are characterized by phases of bone quiescence and healing.

p40 immunohistochemistry is a cornerstone of histopathological examination for non-small cell lung carcinoma. p40 is an isoform of p63 and is reported to be highly specific for the diagnosis of squamous cell carcinoma. Very rare pitfalls are reported for this antibody, and p40 is typically negative in melanoma. A 66-year-old patient was admitted for multiple hemorrhagic brain tumors evocative of secondary tumors. On imaging, a 26 mm lung tumor was detected, and a biopsy of the lung tumor was performed. The tumor was stained by melanic markers and diffusely stained by p40 and p63. Molecular analysis found a somatic p.Asn581Ser (c.1742A>G) point mutation in exon 15 of BRAF and a p.Arg80Ter (c.238C>T) germline variant of CDKN2A, a predisposing mutation to melanoma. This case report highlights the importance of clinical, pathologic, and molecular correlation.