Immunohistochemical Expression Of P53 Research Articles

Rationale for Testing TP53 Mutations in Thyroid Cancer—Original Data and Meta-Analysis

The p53 protein is a tumor-suppressing transcription factor that is critical in tumorigenesis. While TP53 mutations are rare in differentiated thyroid cancer (DTC), they are significantly more common in anaplastic thyroid cancer (ATC). This study presents original results and a meta-analysis reevaluating the prognostic value of TP53 mutations in thyroid cancer, including surrogate markers such as immunohistochemical p53 expression and serum p53-Abs levels. TP53 mutations were analyzed using SSSP and direct sequencing in a DTC group (15 patients), an ATC group (3 patients), and a control group (25 patients). The immunohistochemical p53 expression was assessed in tissue samples. A meta-analysis of 14 eligible studies identified through the PubMed, Scopus, Google Scholar, and Cochrane databases was conducted. Our results showed TP53 mutations in all ATC cases, 6.67% of DTC cases (1 out of 15), and none in the control group. Immunohistochemical p53 overexpression was observed in 4 out of 15 DTC (26.67%) and all ATC cases but absent in controls. A meta-analysis confirmed that TP53 mutations are significantly more frequent in ATC than controls (OR 8.95; 95% CI: 1.36–58.70; p = 0.02) but not in DTC vs. controls (OR 1.87; 95% CI: 0.53–6.58; p = 0.33). p53 overexpression was significantly higher in both DTC and ATC vs. controls (OR 7.99; 95% CI: 5.11–12.51; p < 0.01 and OR 64.37; 95% CI: 27.28–151.89; p < 0.01, respectively). The serum p53-Abs positivity was also elevated in patients with PTC vs. controls (OR 2.07; 95% CI: 1.24–3.47; p < 0.01). TP53 mutations are frequent events in the pathogenesis of ATC. In DTC, further prospective studies are needed to determine the prognostic value of TP53 mutations and related surrogate markers (immunohistochemical p53 expression, p53-Abs positivity).

Verruciform Acanthotic Vulvar Intraepithelial Neoplasia Harbors Recurrent Genomic Alterations Found in HPV-independent Squamous Cell Carcinoma.

The term verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN) was coined to describe HPV-independent p53-wildtype lesions with characteristic clinicopathologic characteristics and association with vulvar squamous cell carcinoma (vSCC). We aimed to expand on the molecular landscape of vaVIN using comprehensive sequencing and copy number variation profiling. vaVIN diagnosis in institutional cases was confirmed by a second review, plus negative p16 and wildtype p53 by immunohistochemistry. Multigene next-generation sequencing and shallow-whole genome sequencing were used to survey for single-nucleotide variants (SNV), copy number alterations, and structural variants. Targeted TERT promoter sequencing was also carried out. Nineteen patients with vaVIN were included; 4 had concurrent vSCC. The median patient age was 74 (range 56-90) years. Genomic aberrations were noted in 18 cases (95%) as follows: PIK3CA in 10 (53%), CDKN2A in 7 (37%), HRAS in 6 (32%), FAT1 and NOTCH1-2 in 5 each (26%), TSC2 in 2 (11%), and PTEN, ARID2, and KRAS in 1 (5%) each. TERT promoter variants were detected in 11 of 13 cases successfully tested (85%). Five vaVINs harbored a TP53 variant but showed wild-type p53 immunohistochemical expression. In one of these, the concurrent carcinoma showed abnormal p53 and biallelic TP53 mutations. Out of 15 patients with follow-up (mean: 20, range: 2-50mo), vaVIN persistence/recurrence was seen in 8 (53%), and subsequent vSCC in 2 (13%). At the last encounter, 3 (20%) patients had persistent disease and 1 (7%) died of vSCC. vaVIN is characterized by a wider molecular spectrum, beyond known alterations in PIK3CA, HRAS, and ARID2, to include TERT promoter, CDKN2A, FAT1, and NOTCH1-2, which are characteristic of HPV-independent vSCC. vaVIN can occur with concurrent or subsequent carcinoma, sometimes with fatal outcomes. These findings support the concept of vaVIN as a neoplastic process within the family of HPV-independent vulvar neoplasia.

The p16 Immunostaining Predicts the Risk of Recurrence in Prostate Cancer.

This study aimed to investigate the influence of p16 immunohistochemical expression on the biochemical recurrence rate of pT2-pT3 prostate cancer. A total of 488 pT2-pT3 stage prostate adenocarcinomas undergoing radical prostatectomy were included in this study. Following a review of Gleason classification and retrieval of sociodemographic and clinicopathological data, as well as the date of last consultation and biochemical recurrence, immunohistochemistry for p16 was performed. Data were associated using the chi-square test, Fisher's exact test, and multinomial logistic regression model. A total of 432(94.5%) cases showed positivity for p16 with an average of 37.38±27.32% positive cells and a mean histoscore of 2.70±2.24. A total of 117 (18.4%) patients experienced biochemical recurrence within three years, which was directly associated with high preoperative PSA (p=0.007), positive surgical margins (p<0.001), pT3 staging (p<0.001), nodal involvement (p<0.001), Gleason score > 3+4 (p<0.001), <50% positivity for p16 (p=0.035), and histoscore p16 =<3 (p=0.004). In multivariate analysis, Gleason score > 3+4 (HR = 3.08 (95% CI = 1.69-5.62), positive surgical margins (HR = 2.93 (95% CI = 1.70-5.04), and histoscore p16 =<3 (HR = 2.49 (95% CI = 1.17-5.32) were predictors of biochemical recurrence within three years. p16 immunostaining, along with classical features such as Gleason Score and surgical margin involvement, are significant predictors of biochemical recurrence in pT2-pT3 prostate tumors.

COMPARATIVE EVALUATION OF P53 IN NORMAL BREAST, FIBROADENOMA, AND CARCINOMA BREAST

Objectives: The objective of this study was to analyze as well as compare the immunohistochemical expression of P53 in normal breast tissue and cases of fibroadenoma and carcinoma breast. Methods: The present study was a retrospective analysis over a period of 1 year (2022–2023). A total of 60 cases comprising 10 cases of normal breast tissue, 20 cases of fibroadenoma breast, and 30 cases of carcinoma breast were included. Immunohistochemical staining by P53 antigen was performed and slides were graded accordingly as Grade 0, 1, and 2 depending on the staining intensity and percentage. Results: Correlation of P53 staining across the spectrum of normal breast, fibroadenoma, and carcinoma breast showed a significant association (p=0.01). There was no significant association between the age and level of P53 expression (p=0.1). On evaluating the association between other clinicopathological variables and grade of P53 expression, we found a significant association with regards to tumor size (p=0.0006), tumor grade (p=0.043), lymph-vascular invasion (p=0.019), and nodal metastasis (p=0.025). Conclusion: P53 may be a possible prognostic marker, to help in better therapeutic management of cases of breast carcinoma.

Olıgosarcoma: A Rare Case Report Wıth Dıstınct Features.

Oligosarcoma is a recently identified entity characterized by sarcomatous changes originating from oligodendroglioma. As of our current understanding, sarcomatous components are infrequent in glial tumors. The World Health Organization (WHO) classification describes sarcomatous features as a rare pattern in grade 3 oligodendrogliomas. In this report, we present a 42-year-old man diagnosed with oligosarcoma. The patient initially presented with a lesion in the right parietotemporal area 9 years ago, and the pathological diagnosis was oligodendroglioma. Nine years later, a recurrent lesion in the same area was observed. Histomorphological evaluation of the recurrent lesion revealed distinct glial and sarcomatous components. The diagnosis of oligosarcoma was made based on histologic assessment; however, additional histochemical (reticulin-rich sarcomatous area), immunohistochemical, and molecular evaluations were also conducted. Immunohistochemical marker expression patterns in oligosarcoma have been reported variably in the literature. In our patient, the sarcomatous component exhibited p53 and OLIG2 immunohistochemical expression. Molecular analysis revealed IDH and TERT mutations, as well as 1p/19q and CDKN2A deletions.

Immunohistochemical expression of P53, Ki-67, and CD34 in psoriasis and psoriasiform dermatitis

Immunohistochemical expression of P53, Ki-67, and CD34 in psoriasis and psoriasiform dermatitis

Assessment of P16 and Ki-67 Proteins Immunoexpressing in Oral Mucosa Among Saudi Smokers.

It is widely known that tobacco use significantly contributes to a variety of health problems, including mouth cancer. The proteins P16 and Ki-67 have a role in regulating the cell cycle and promoting cell growth. Analyzing the levels of these proteins can give us valuable information about the overall health of cells. This study aims to assess the cellular alterations and immunohistochemical expression of P16 and Ki-67 in the oral mucosa of Saudi smokers. From March to December 2023, a cross-sectional study scraped 500 samples from the buccal mucosa. Participants in the study were Saudi citizens of both genders. We selected a total of 300 individuals who smoked cigarettes and 200 individuals who did not smoke tobacco as the control group. The selection process involved two sample techniques: initially purposive sampling and subsequently snowball sampling. The samples underwent an immunohistochemical examination to determine the presence of P16 and Ki-67 protein overexpression. We evaluated the samples by assessing the proportion of cells that exhibited positive staining and the intensity of the staining. The data were examined utilizing SPSS. We identified categorical variables by calculating frequencies and percentages using the chi-squared test. A significance level of p < 0.05 was used to determine statistical significance. A total of 48% of cigarette users had abnormal results, compared to 20% of nonsmokers. These abnormalities included cytological atypia, inflammation, reverse cytological infection, and binucleated or multinucleated cells (p = 0.015). People who smoked had higher levels of P16 and Ki-67 expressions than people who did not smoke, 12% and 5%, respectively (p = 0.042). There were no important changes in P16/Ki-67 expression between participants of different ages (p = 0.68) or between men and women (p = 0.27). These results demonstrate the detrimental effects of smoking on cell health, underscoring the importance of quitting to reduce the risk of cytological abnormalities and related diseases. Smokers have higher levels of the proteins P16 and Ki-67, which shows how important these biomarkers are for understanding the risks to oral health.

EXPRESSION OF p16 AND Ki-67 IN ORAL SQUAMOUS CELL CARCINOMA

Introduction:Oral Squamous Cell Carcinomais a major health challenge with high recurrence and poor prognosis.Asper Globocan 2022, lip and oral cancer ranked 16th in terms of incidence with 389,485(2%)newcases. p16 helps identify HPV infection and induces apoptosis, while Ki-67, a key cell cycle regulator, is crucial for assessing cell proliferation, tumor development and prognosis. Aim: The study aims to evaluate the immunohistochemical expression of p16 and Ki-67 in oral squamous cell carcinoma and correlation with various clinicopathological parameters. Material and Methods: This descriptive analysis was conducted at Muzaffarnagar Medical College &amp; Hospital, involving 50 histologically confirmed oral squamous cell carcinoma cases. The study involved p16 and Ki-67 expression through immunohistochemistry on histologically diagnosed OSCC cases and scoring was done. Results: The study found that most OSCC patients belong to fifth and sixth decades of life, with buccal mucosa being the most affected site. Tobacco use was prevalent among the patients. Most cases were moderately differentiated. p16 and Ki-67 expression werehigher in poorly differentiated cases. Positive p16 expression was observed in 38% of the cases but showed no significant correlation with age, gender, or histological grade. However, significant associations were found between age, histological grade, and Ki-67 expression. Conclusion: This study concluded that p16 expression was positive in 38% of OSCC cases, with higher rates in poorly differentiated tumors, but no significant links to age, gender, or histological grade. Ki-67 levels, higher in poorly differentiated cases, were significantly associated with age, indicating more aggressive disease in older ones.

Relevance of the Immunohistochemical Expression of p53 and E-cadherin in the Grading of Urothelial Carcinoma: A Single-Center Cross-Sectional Observational Study.

Background Urothelial carcinoma (UC) is a prevalent cancer worldwide, primarily affecting the urinary bladder. It is more common in men than women and is often linked to factors like tobacco smoking, occupational exposure, and chronic infections. UC can be classified into different subtypes based on its growth pattern (papillary or non-papillary) and the extent of invasion into the bladder wall. The management of UC depends on its grade and stage, with treatment options ranging from transurethral resection of bladder tumor (TURBT) for non-invasive tumors to cystectomy for muscle-invasive disease. This study aimed to investigate the expression of p53 and E-cadherin in low-grade and high-grade UC and their correlation with histomorphological parameters. Materials and methods A cross-sectional observational study was conducted on 50 histopathologically confirmed UC cases. Immunohistochemical (IHC) staining for p53 and E-cadherin was performed, and the results were correlated with clinicopathological features. Statistical analysis was performed to find the correlation between p53 and E-cadherin immunoexpression and the grade of UC. Results The cohort's mean age was 58.18±12.99 years, with a male predominance (76%). Most cases (52%) were from rural areas and unskilled workers (52%). Hematuria was present in all cases (100%), while urgency and frequency were reported in 32% each. High-grade UC was more common (76%), with 48% being invasive. Muscle invasion was absent in 56%. p53 overexpression was seen in all cases, with 38% moderate and 36% strong staining. Twenty-two out of 24 cases (91.7%) of invasive UC showed low E-cadherin expression, while all 26 cases (100%) of low-grade papillary UC and high-grade papillary UC displayed high E-cadherin expression. This suggests that reduced E-cadherin expression is strongly associated with invasive UC, potentially as a tumor aggressiveness and progression marker. Conclusion Considering that elevated p53 protein expression is linked to aggressive tumor behavior, a more intensive treatment strategy is recommended for patients with non-muscle-invasive bladder cancer (NMIBC) who show high p53 protein scores. On the other hand, the downregulation or absence of E-cadherin expression has been recognized as a strong indicator of advanced grade and higher clinical stages.

Prognostic and predictive significance of p53 and ATRX in neuroendocrine neoplasms of GIT and pancreas and their utility as an adjunct to accurate diagnosis-An eight-year retrospective study.

Neuroendocrine neoplasms of gastrointestinal tract (GIT)and pancreas are heterogenous tumors. World Health Organization (WHO)2019 classification introduced Grade (G)3 neuroendocrine tumor (NET) distinct from neuroendocrine carcinoma (NEC), based on molecular differences and to triage the patients for appropriate therapy. This distinction largely relies on morphology, which can be challenging at times. Genomic profiling has revealed TP53andRB1mutations in NECs, while death domain-associated protein 6 (DAXX) and alpha-thalassemia/mental retardation X-linked (ATRX),in G3NET. Their role as biological markers in differentiating these entities and their significance as prognostic markers are not yet established. This study aims at analyzing the diagnostic and prognostic role of p53 and ATRX in neuroendocrine neoplasms of GIT and pancreas. A single-centre, eight-year retrospective study of neuroendocrine neoplasm of GIT and pancreas comprised G2NET, G3NET and NEC. Tumor slides were stained by immunohistochemistry for p53 and ATRX. Strong nuclear staining of > 50% of tumor cells for p53 was considered mutated. Nuclear staining of ATRX in < 5% of tumor cells was considered ATRX loss. Expression of p53 and ATRX was analyzed and correlated with tumor grades and patient survival. Fifty-five patients with gastro-entero-pancreatic neuroendocrine neoplasm were studied, comprising G2NET (58%), G3NET (16%) and NEC (26%). Median age of diagnosis was 59years with male predominance. The pancreas was the most common site followed by the small bowel. NEC showed lower survival compared to G3 and G2NET. Mutated p53 immunohistochemical expression was more frequent among NEC than G3NET. Patients with mutated p53 had significantly lower survival irrespective of the grade (p = 0.001). There was no association of ATRX loss with grade or survival. G3NETs are genetically different from NECs. Use of immunohistochemistry for p53 in addition to histomorphology may facilitate accurate categorization of NEC and G3NET. Mutated p53 may also be used as an independent prognostic marker in neuroendocrine tumors of GIT and pancreas.

Immunohistochemical Expression of p53 and FGFR3 Predicts Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma.

Locally advanced or metastatic urothelial carcinoma is a genomically and molecularly heterogeneous disease associated with various clinical outcomes. We aimed to evaluate the association between the status of p53/FGFR3 expression and the efficacy of enfortumab vedotin (EV) in metastatic urothelial carcinoma. We evaluated the association between p53 (abnormal vs. wild-type) or FGFR3 (high vs. low) expression determined by immunohistochemistry and response to EV in 28 patients with metastatic urothelial carcinoma. Overall, 60.7% showed abnormal p53, and 17.9% had high FGFR3 expression. The rates of objective response to EV were statistically higher in patients with abnormal p53 than in those with wild-type p53 (p = 0.038). Patients with pure urothelial carcinoma (n = 18) and low FGFR3 showed significantly better response to EV than those with high FGFR3. When the statuses of p53 and FGFR3 were combined, abnormal p53/low FGFR3 (vs. wild-type p53/high FGFR3) was strongly associated with favorable outcomes in both the entire cohort (p = 0.002) and in cases of pure urothelial carcinoma only (p = 0.023). Immunohistochemically abnormal p53 tumors were found to respond well to EV, while high FGFR3 tumors had a poorer response. Thus, p53 and FGFR3 are potential biomarkers for predicting response to EV treatment in patients with urothelial carcinoma.

Prognostic Importance of PTEN, p53, and MDM2 Expressions in Endometrioid and Serous-Type Endometrial Carcinomas

Aim: Endometrial carcinomas (ECs) are neoplasms with the highest rate of change in the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. In this study, the relationship among PTEN, MDM2, and p53 protein expression in the PI3K/AKT/mTOR pathway with clinicopathological data in endometrioid endometrial carcinomas (EECs) and serous-type endometrial carcinomas (SECs) was evaluated. Material and Method: A hundred and twenty cases of patients who underwent hysterectomy for EC between 2009 and 2021 were included in the study. Thirty cases of SEC and 90 cases of EEC were evaluated. EEC cases consist of grades 1-3 tumors, and each group includes 30 patients. p53 was examined in two groups as normal/wild type and abnormal/mutant type. PTEN and MDM2 were examined in two groups: positive and negative. The relationship among p53, PTEN, and MDM2 immunohistochemical expression status with histological grade, myometrial invasion, cervical invasion, lymphovascular invasion (LVI), metastatic lymph nodes, presence of tumor in peritoneal fluid, tumor stage, and overall and progression-free survival was evaluated. Results: Loss of PTEN was associated with EEC compared to SEC (p

Diagnostic Accuracy of Immunohistochemical Expression of p16, MDM2, and CDK4 in Well-Differentiated and De-Differentiated Liposarcoma in MDM2 Fluorescent in situ Hybridisation Confirmed Cases.

To establish the diagnostic utility of immunohistochemistry markers p16 along with MDM2 and CDK-4 in confirming the diagnosis of well-differentiated and de-differentiated liposarcoma while taking Fluorescent in situ Hybridisation (FISH) as a gold standard. A cross-sectional study. Place and Duration of the Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from 30th January 2022 to 30th June 2023. A standard panel of three immunohistochemistry markers p16, MDM2, and CDK4 were applied to 36 cases of atypical lipomatous tumours, well-differentiated liposarcoma (WDLPS), and de-differentiated liposarcoma (DDLPS), on which the gold standard FISH was already performed. The sample size was calculated with the help of a WHO calculator taking prevalence 1-2% in Pakistani population. Qualitative variables such as gender and site of tumour were presented by calculating frequency and percentages and comparison of Immunohistochemistry results with FISH was done by using a 2x2 table. The sensitivity and specificity of this triple marker panel for detecting WDLPS/DDLPS were 43.47% and 15.38%, respectively. The sensitivity and specificity of CDK4 for detecting WDLPS / DDLPS were 82.6% and 15.4%, those of MDM2 were 73.9% and 61.5 %, and those of p16 were 60.9% and 53.8%, respectively. Among all three markers, CDK4 was the most sensitive and MDM2 was the most specific marker for detecting WDLPS-DDLPS. It also showed that a combination of these three markers improves the diagnostic credibility of the immunohistochemistry in diagnosing DDLPS and WDLPS but FISH is the most reliable and confirmatory method. De-differentiated liposarcoma, Well-differentiated liposarcoma, P16, CDK4, MDM2.

The Sensitivity of Immunohistochemical Expression of p53 as an Indicator of the Malignant Potential of Gastric Hyperplastic Polyps: A Retrospective Study

Background: Hyperplastic polyps account for 30–93% of gastric polyps. Recently, there have been studies about the development of dysplasia in this type of polyp. Every cell in the body contains the p53 gene, which has anti-cancer properties. Objective: The sensitivity of immunohistochemical expression of p53 is evaluated among gastric hyperplastic polyps with and without dysplasia and gastric adenomatous polyps to know its usefulness as a diagnostic marker. Methods: A retrospective cross-sectional study was done on fifty formalin-fixed paraffin-embedded blocks of gastric polyps (44 hyperplastic polyps without dysplasia, 3 hyperplastic polyps with dysplasia, and 3 adenomas). Cases were collected from the archives of the pathology department from June 2019 to July 2023. Additional sections of the block were immunostained with P53 protein. Results: Fifty paraffin blocks from patients with gastric polyps (17 males, 33 females) were included in the study. 44 of the cases are classified as hyperplastic polyps, 3 as hyperplastic polyps with dysplasia, and 3 as adenomatous polyps. Most gastric hyperplastic polyps showed staining in different scores. All gastric hyperplastic polyps with dysplasia showed nuclear staining, whereas two out of three gastric adenomatous polyps showed no staining. Conclusion: There was no significant association between p53 protein expression and the type of gastric polyps, the presence of intestinal metaplasia, or H. pylori. However, it has a significant correlation with the size of the polyps.

Evaluation of Immunohistochemical Expression of p53 in Colorectal Carcinoma

Evaluation of Immunohistochemical Expression of p53 in Colorectal Carcinoma

Redefining aberrant P53 expression of gastric cancer and its distinct clinical significance among molecular-histologic subtypes

BackgroundNumerous studies have demonstrated a correlation between p53 overexpression and diminished survival in gastric cancer patients. However, conflicting findings exist, and we hypothesize that these discrepancies arise from the cancer's complexity and heterogeneity, coupled with a lack of consensus on aberrant p53 expression. MethodsWe enrolled a cohort of 187 patients with surgically resected gastric cancer. Patient categorization was based on Epstein–Barr virus (EBV), microsatellite instability (MSI), and Lauren classification (intestinal, diffuse and mixed). Utilizing an incremental algorithm, we evaluated p53 immunohistochemical (IHC) patterns in all 187 cases, while next-generation sequencing was successfully performed on 152 cases to identify TP53 mutations (mutTP53). ResultsMutTP53 was identified in 32 % of the 152 cases, comprising 36 missense, 5 nonsense, and 7 frameshift alterations. Missense mutations predominantly correlated with p53 overexpression, while nonsense and frameshifting alterations related to null expression. Trial calculations indicated that null expression and a p53 IHC cutoff at >40 % offered the best prediction of mutTP53 (kappa coefficient, 0.427), with the highest agreement (0.524) observed in diffuse type and the lowest (0.269) in intestinal type. Null expression and a p53 IHC cutoff at >10 %, but not mutTP53 per se, provided the optimal prediction of survival outcome (p = 0.043), particularly in diffuse type (p = 0.044). Multivariate analysis showed that aberrant p53 IHC expression was not an independent prognostic factor. ConclusionsP53 IHC patterns are predictive biomarkers for mutTP53 and gastric cancer outcomes, where a prerequisite involves a nuanced approach considering cutoff values and molecular-histologic subtyping.

Effect of p16 immunohistochemical expression (exp) on irinotecan in metastatic colorectal cancer (mCRC): A translational analysis of the TRIBE and TRIBE2 studies.

3562 Background: CDKN2A encodes the inhibitor of the cyclin-dependent kinases p16 and is frequently methylated in colorectal cancer, thus reducing the exp levels of p16 protein. In pre-clinical models of colorectal cancer cells, the demethylation of CDKN2A gene induces topoisomerase I upregulation increasing the sensitivity to irinotecan. In metastatic colorectal cancer (mCRC) pts, the role of p16 expression has been poorly investigated. Methods: Tumour samples of pts randomized in the phase III TRIBE2 study comparing upfront FOLFOXIRI/bevacizumab (bev) versus (vs) FOLFOX/bev were assessed for p16 immunohistochemical exp. A validation analysis in patients treated with FOLFIRI/bev in the TRIBE study was conducted. Results: Out of 679 patients enrolled in the TRIBE2 study, 231 tumours were assessed for p16 exp. Overall, 152 (66%), and 79 (34%) were classified as positive (pos) (IHC 2+ and 3+) and negative (neg) (IHC 0 and 1+), respectively. In the p16 pos group, 69 (45%) and 83 (55%) pts received FOLFOXIRI/bev and FOLFOX/bev, respectively, while in the p16 neg cohort, FOLFOXIRI/bev was administered in 37 (47%) and FOLFOX/bev in 42 (53%) cases. Pts with p16 neg tumours had more frequently an ECOG-PS of 1-2 (16% vs 6%, p=0.0098) and a BRAF mut tumour (26% vs 7%, p=0.0002). No PFS difference was observed between p16 neg and pos patients, while a trend for a longer OS was shown in favour of p16 pos pts (25.5 vs 21.3 months; HR: 0.74, 95%CI: 0.53-1.02, p=0.068) that was not confirmed at the multivariate analysis (p=0.61). Among patients with p16 pos tumours, those treated with FOLFOXIRI/bev reported longer PFS (12.8 vs 9.4 months, HR: 0.55, 95%CI: 0.39-0.78, p=0.0008) and OS (30.0 vs 21.4 months, HR: 0.66, 95%CI: 0.46-0.95, p=0.026) than those receiving FOLFOX/bev. On the other hand, no significant difference was observed among p16 neg patients in terms of both PFS (9.0 vs 9.4 months, HR: 0.91, 95%CI: 0.57-1.46, p=0.69) and OS (21.3 vs 19.5 months, HR: 0.95, 95%CI: 0.58-1.57, p=0.85), thus suggesting a differential treatment effect according to p16 exp (pinteraction for PFS =0.12; pinteraction for OS =0.19). Among patients treated with FOLFIRI/bev in the TRIBE study (N=58) patients with p16 pos tumours reported longer PFS and OS than those with p16 neg. (HR for PFS: 0.45, 95%CI: 0.22-0.92, p=0.026; HR for OS: 0.41, 95%CI: 0.20-0.85, p=0.013). Conclusions: In mCRC, p16 pos exp seems associated with higher benefit from irinotecan. Prospective confirmation in independent randomized series is warranted.

Cytoplasmic PPARγ Significantly Correlates With P53 Immunohistochemical Expression and Tumor Size in Localized Tenosynovial Giant Cell Tumor.

Tenosynovial giant cell tumor (TGCT)is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths.It has an inflammatory neoplastic nature, with a clinical presentationranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized formsof TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient's quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets. The study is cross-sectional, in which 27 LTGCT cases were collectedfrom the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed. All the 27 collected LTGCT cases were located in the small joints of patients' hands. Cases with solitary LGTCTs constituted 55.6%(n = 15), while 44.4% (n = 12) had multipleLTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity. PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

High-Risk HPV CISH Detection in Cervical Biopsies with Weak and/or Focal p16 Immunohistochemical Positivity.

In cervical biopsies, for diagnosis of Human Papilloma Virus (HPV) related conditions, the immunohistochemical staining for p16 has a diagnostic value only if diffusely and strongly positive, pattern named "block-like". "Weak and/or focal (w/f) p16 expression" is commonly considered nonspecific. In our previous study, we demonstrated the presence of high-risk HPV (hrHPV) DNA by LiPa method in biopsies showing w/f p16 positivity. The aim of the present study was to investigate the presence of hrHPV-DNA by CISH in the areas showing w/f p16 expression. We assessed the presence of hrHPV16, 18, 31, 33, 51 by CISH in a group of 20 cervical biopsies showing w/f p16 expression, some with increased Ki67, and in 10 cases of block-like expression, employed as control. The immunohistochemical p16 expression was also assessed by digital pathology. hrHPV-CISH nuclear positivity was encountered in 12/20 cases of w/f p16 expression (60%). Different patterns of nuclear positivity were identified, classified as punctate, diffuse and mixed, with different epithelial distributions. Our results, albeit in a limited casuistry, show the presence of HPV in an integrated status highlighted by CISH in w/f p16 positive cases. This could suggest the necessity of a careful follow-up of the patients with "weak" and/or "focal" immunohistochemical patterns of p16, mainly in cases of increased Ki67 cell proliferation index, supplemented with molecular biology examinations.

Immunohistochemical (IHC) Expression of p16 in Various Grades of Oral Squamous Cell Carcinoma (OSCC) with Snuff Use in Tertiary Care Hospitals of Peshawar

Oral squamous cell carcinoma (OSCC) is a significant health concern, with various factors influencing its development and progression. Understanding these factors, including p16 expression and clinicopathologic features, is crucial for improved diagnosis and treatment. Objective: To compare various grades of OSCC based on immunohistochemical expression of p16 and clinicopathologic parameters. Methods: The comparative cross-sectional study was conducted at the Department of Pathology, Peshawar Medical College (PMC), and Peshawar Dental College (PDC) from August 2020 to August 2021. It included 53 cases of OSCC with documented snuff use history. Tumor sections were stained with Hematoxylin and Eosin and underwent immunohistochemical staining for p16 expression. Sample size calculation utilized G Power software. Statistical analysis was performed using SPSS version 20.0, employing the Chi-Square test to assess categorical variables. Results: Among the 53 OSCC cases, the majority were male (66.0%) with ages ranging from 26 to 85 years, the most common age group being 51-70 years. The tongue was the primary site for OSCC development. Well-differentiated cases were predominant (64.2%), followed by moderate (20.8%) and poor grade cases (15.1%). However, no significant association was found between p16 expression and OSCC grades. Notably, p16 expression tended to be higher in snuff users and well-differentiated OSCC cases, although not statistically significant. Conclusions: Well-differentiated OSCC cases exhibited the highest expression of p16, followed by moderate and poorly differentiated cases. However, no significant correlation was observed between p16 expression and OSCC in snuff users.