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Arkhiv Patologii 2024The purpose of this work was to evaluate gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the...
OBJECTIVE
The purpose of this work was to evaluate gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor.
MATERIAL AND METHODS
The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe.
RESULTS
In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (<0.05).
CONCLUSION
Amplification of the gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.
Topics: Humans; Male; Prostatic Neoplasms; Proto-Oncogene Proteins c-myc; Gene Amplification; Middle Aged; Aged; Genes, myc; Carcinoma, Acinar Cell
PubMed: 38881003
DOI: 10.17116/patol20248603130 -
Cancer Treatment and Research... Jun 2024Recently, some evidence emphasized the value of MSH2 and MSH6 inactivation and their hypermutation in predicting different cancers. The present consideration is to...
BACKGROUND
Recently, some evidence emphasized the value of MSH2 and MSH6 inactivation and their hypermutation in predicting different cancers. The present consideration is to evaluate the value of MSH2 and MSH6 protein deficient studied by the immunohistochemistry (IHC) method and the tumor behaviors and aggressiveness in prostatic carcinoma.
METHODS
This cross-sectional study was performed on 80 examples extricated from patients who endured prostate cancer and were planned for radical prostatectomy surgery. The expression levels of the genes were studied by IHC staining.
RESULTS
The deficiency in MSH2 and MSH6 expression was revealed in 10.0 % and 11.3 % of patients respectively, while the reduction of simultaneous expression in two genes was found in 6.2 % of patients. In the two subgroups with and without MSH2 and/or MSH6 staining, there was no difference in patients' mean age and history of prostate cancer. There was also no difference in tumor-related behaviors including combined Gleason grade group, tumor stage, vascular invasion, perineural invasion, and prostatic capsular invasion between the groups with and without gene loss.
CONCLUSION
The evaluation of the deficient rate of two genes among patients with prostate cancer to predict the tumor grade and its aggressive behavior needs further study in every population.
PubMed: 38870667
DOI: 10.1016/j.ctarc.2024.100826 -
Aging Jun 2024Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the...
BACKGROUNDS
Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the development and progression of GC as an adhesive, invasive suppressor gene. Whether reduced E-cadherin has an impact on prognosis, clinicopathological features for GC has been well studied, but no conclusive results has been obtained.
METHODS
Eligible studies and relevant data were obtained from PubMed, Elsevier, Embase, Cochrane Library and Web of Science databases until June 30, 2023. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Correlation of E-cadherin expression with overall survival (OS), clinicopathological features and risk factors were evaluated.
RESULTS
36 studies fulfilled the selected criteria. 9048 cases were included. This meta-analysis showed that patients with GC with reduced E-cadherin had unfavourable clinicopathological features and poor OS. The pooled ORs of one-, three- and five-year OS were 0.38 ( = 25 studies, 95%CI: 0.25-0.57, Z = 4.61, < 0.00001), 0.33 ( = 25 studies, 95% CI: 0.23-0.47, Z = 6.22, < 0.00001), 0.27 ( = 22 studies, 95% CI: 0.18-0.41, Z = 6.23, < 0.00001), respectively. Moreover, reduced E-cadherin expression significantly correlated with differentiation grade (OR = 0.29, 95% CI: 0.22-0.39, Z = 8.58, < 0.00001), depth of invasion (OR = 0.49, 95% CI: 0.36-0.66, Z = 4.58, < 0.00001), lymphatic node metastasis (OR = 0.49, 95% CI: 0.38-0.64, Z = 5.38, < 0.00001), distant metastasis (OR = 2.24, 95% CI: 1.62-3.09, Z = 4.88, < 0.00001), peritoneal metastasis (OR = 2.17, 95% CI: 1.39-3.39, Z = 3.40, = 0.0007), TNM stage (OR = 0.41, 95% CI: 0.28-0.61, Z = 4.44, < 0.00001), lymphatic vessel invasion (OR = 1.77, 95% CI: 1.11-2.82, Z = 2.39, = 0.02), vascular invasion (OR = 1.55, 95% CI: 1.22-1.96, Z = 3.58, = 0.0003), Lauren type (OR = 0.35, 95% CI: 0.21-0.57, Z = 4.14, < 0.0001), Borrmann classification (OR = 0.50, 95% CI: 0.25-0.99, Z = 1.97, = 0.048) and tumor size (≥5 cm vs. <5 cm: OR = 1.73, 95% CI: 1.34-2.23, Z = 4.19, < 0.0001; ≥6 cm vs. <6 cm: OR = 2.29, 95% CI: 1.51-3.49, Z = 3.87, = 0.0001). No significant association was observed between reduced E-cadherin expression and liver metastasis, perineural invasion, alcohol consumption, smoking status, familial history, Helicobacter pylori (HP) infection.
CONCLUSIONS
The reduced expression of E-cadherin is significantly correlated with poor OS and unfavourable clinicopathological features in GC. The expression level of E-cadherin not only serves as a predictor for disease progression and prognosis in GC but also emerges as a novel therapeutic target.
PubMed: 38870263
DOI: 10.18632/aging.205929 -
American Journal of Clinical Pathology Jun 2024We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment...
OBJECTIVES
We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC).
METHODS
A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3).
RESULTS
We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2 = 0.3) and significantly associated with MMR-deficient tumors (P < .001); B2M-low tumors were also associated with an "immune cold"' microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P = .018), a finding that maintained significance only for the proficient MMR cohort (P = .037).
CONCLUSIONS
Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma.
PubMed: 38869306
DOI: 10.1093/ajcp/aqae066 -
BJS Open May 2024Endoscopic resection of T1 colon cancer (CC) is currently limited by guidelines related to risk of lymph node metastases. However, clinical outcome following endoscopic...
BACKGROUND
Endoscopic resection of T1 colon cancer (CC) is currently limited by guidelines related to risk of lymph node metastases. However, clinical outcome following endoscopic and surgical resection is poorly investigated.
METHOD
A retrospective multicentre national cohort study was conducted on prospectively collected data from the Swedish colorectal cancer registry on all non-pedunculated T1 CC patients undergoing surgical and endoscopic resection between 2009 and 2021. Patients were categorized on the basis of deep submucosal invasion (Sm2-3), lymphovascular invasion (LVI), poor tumour differentiation, and R1/Rx into low- and high-risk cases. The primary outcomes of interest were recurrence rates and disease-free interval (DFI, defined as time from treatment to date of recurrence) according to resection methods and risk factors (sex, age at diagnosis, histologic grade, LVI, perineural invasion, mucinous subtype, submucosal invasion, tumour location, resection margin and nodal positivity in the surgical group).
RESULTS
In total, 1805 patients undergoing endoscopic (488) and surgical (1317) resection with 60.0 months median follow-up were included. Recurrence occurred in 18 (3.7%) endoscopically and 48 (3.6%) surgically resected patients. Adjuvant treatment was administered in 7.4% and 0.2% of the cases respectively in the surgical and endoscopically treated patients. Five-year DFI was 95.6% after endoscopic and 96.2% after surgical resection, with no significant difference when adjusting for confounding factors (HR 1.03, 95% c.i. 0.56 to 1.91, P = 0.920). There were no statistically significant differences in recurrence comparing endoscopic (1.7%) versus surgical (3.6%) low-risk and endoscopic (5.4%) versus surgical (3.8%) high-risk cases. LVI was the only significant risk factor for recurrence in multivariate Cox regression (HR 3.73, 95% c.i. 1.76 to 7.92, P < 0.001).
CONCLUSIONS
This study shows no difference in recurrence after endoscopic and surgical resection in high-risk T1 CC. Although it was not possible to match groups according to treatment, the multivariate analysis showed that lymphovascular invasion was the only independent risk factor for recurrence.
Topics: Humans; Male; Female; Neoplasm Recurrence, Local; Aged; Registries; Colonic Neoplasms; Retrospective Studies; Middle Aged; Sweden; Risk Factors; Aged, 80 and over; Lymphatic Metastasis; Colonoscopy; Neoplasm Staging; Neoplasm Invasiveness; Colectomy
PubMed: 38869239
DOI: 10.1093/bjsopen/zrae053 -
Head & Neck Jun 2024Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to...
BACKGROUND
Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China.
METHODS
A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index.
RESULTS
Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model.
CONCLUSION
We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.
PubMed: 38867407
DOI: 10.1002/hed.27818 -
Iranian Journal of Pathology 2024Colorectal cancer is the second reason for cancer-associated death. The prognosis of the malignancy is defined by TNM scoring. However, tumor grading, lymphovascular...
BACKGROUND & OBJECTIVE
Colorectal cancer is the second reason for cancer-associated death. The prognosis of the malignancy is defined by TNM scoring. However, tumor grading, lymphovascular invasion, perineural invasion, and tumor buddings may affect its prognosis. This study aimed to assess the prognostic and histologic impact of tumor budding in colorectal adenocarcinoma.
METHODS
This study is a retrospective cohort of 192 patients with colorectal adenocarcinoma. All four stages of colorectal adenocarcinoma patients were included, but the patients in stages I and II were also analyzed separately. We used pathology reports to extract the histopathologic data. The prognostic values were extracted by calling the patients.
RESULTS
Less than half of the patients were in stages I and II of the disease. According to our analysis, tumor extension and lymphovascular invasion were correlated with tumor budding count in patients in stages I and II, and lymphovascular invasion, tumor grade, tumor stage, lymph node involvement, tumor extension, tumor site, metastasis, and five-year survival were correlated with tumor budding within all stages.
CONCLUSION
It is recommended that tumor budding count should be assessed and reported in pathology reports of adenocarcinomas due to its high correlation with poor prognosis.
PubMed: 38864085
DOI: 10.30699/IJP.2023.1999329.3090 -
Iranian Journal of Pathology 2024Bladder carcinoma ranks second in prevalence among males in Egypt. As a family of tyrosine kinases, fibroblast growth factor receptor (FGFR) dysregulation has been...
BACKGROUND & OBJECTIVE
Bladder carcinoma ranks second in prevalence among males in Egypt. As a family of tyrosine kinases, fibroblast growth factor receptor (FGFR) dysregulation has been linked to some malignancies in humans. The aim of this study is to analyze the clinicopathological data of patients while investigating FGFR2 and FGFR3 immunohistochemical expression in invasive urothelial bladder carcinoma.
METHODS
This retrospective cross-sectional study included 60 invasive urothelial carcinoma (UC) cases in the Pathology department, Faculty of Medicine, Menoufia University, from 2009 to 2020. All biopsies were stained for FGFR2 and FGFR3 antibodies. Complete clinical data were available for 44 patients treated and followed in clinical oncology and nuclear medicine departments.
RESULTS
Advanced stage and high grade are significantly correlated with FGFR2 positivity (=0.048 and 0.044, respectively). Cases presented with Perineural invasion showed a higher percentage of FGFR2 (=0.023). There is a significant indirect linear correlation between FGFR3 expression and lymph node positivity (r= -0.265, =0.041).
CONCLUSION
A high FGFR2 expression could be associated with poor prognostic parameters, while high FGFR3 expression would be associated with good prognostic parameters. These findings might highlight the importance of FGFR-targeted therapy as a FGFR2 antagonist and FGFR3 agonist for the treatment of urothelial carcinoma patients.
PubMed: 38864084
DOI: 10.30699/IJP.2024.2012115.3180 -
Iranian Journal of Pathology 2024Colorectal carcinoma (CRC) is one of the most common cancers worldwide. The interaction of programmed cell death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1)...
BACKGROUND & OBJECTIVE
Colorectal carcinoma (CRC) is one of the most common cancers worldwide. The interaction of programmed cell death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) plays an important role by inhibiting the immune mechanism by which cancer cells escape antitumor immunity. Immunotherapy using checkpoint inhibitors is a growing treatment modality in many cancers; one such is anti-PD1/PD-L1. The present study aimed to study the immunohistochemical (IHC) expression of PD-L1 in CRC and its association with various known clinicopathological parameters.
METHODS
This study was a 2-year prospective study and included 34 colectomy specimens diagnosed as colorectal adenocarcinoma. The expression of PD-L1 was evaluated on tumoral cells and tumor-infiltrating immune cells (TIICs) and was correlated with various clinicopathological parameters.
RESULTS
Immunohistochemical expression of PD-L1 on tumoral cells and tumor microenvironment in CRC revealed positivity in 17.65% of cases each. The PD-L1 expression on tumoral cells was associated with lymphovascular invasion (LVI) and perineural invasion (PNI) with P- values of 0.012 and 0.005, respectively, while PD-L1 expression on TIICs was associated with tumor budding with a P-value of 0.022.
CONCLUSION
IHC expression of PD-L1 on tumoral cells and immune cells may be associated with some known poor prognostic factors. Since anti-PD1/PD-L1 is used for targeted therapy, it may be beneficial and economically feasible to evaluate PD-L1 in CRC and establish its role as a prognostic factor.
PubMed: 38864082
DOI: 10.30699/IJP.2023.1988660.3054 -
Iranian Journal of Pathology 2024Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was...
BACKGROUND & OBJECTIVE
Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was conducted to investigate the immunohistochemical overexpression of p16, a surrogate marker for HPV, and to evaluate its usefulness as a potential diagnostic biomarker.
METHODS
In this cross-sectional prospective and retrospective cohort study, 56 penile squamous cell carcinoma (SCC) specimens and five penile premalignant specimens were evaluated in Kasturba Medical College, Mangalore, India, from January 2013- December 2018 in terms of clinical and histopathological features. Immunohistochemical expression for p16 in cases and controls was evaluated. Statistical comparison of p16 expression among clinical features, histological subtype, grade, and stages of tumor were done.
RESULTS
Analysis of the pattern of p16 staining showed diffuse and strong nuclear and cytoplasmic expression in 32.8% of the cases. There was a highly significant association (<0.001) of pattern of p16 expression among the HPV and non-HPV subtypes of penile carcinoma. p16 expression was not significantly associated with other prognostic parameters like site of the lesion, lymphovascular invasion, perineural invasion, histologic grade, and pathologic stage.
CONCLUSION
Expression of p16 would be a useful tool in differentiation between the HPV-associated and non-HPV-associated subtypes of penile SCC that may be helpful in prediction of aggressiveness and invasive potential of the respective histologic subtypes.
PubMed: 38864076
DOI: 10.30699/IJP.2024.1998898.3092