Clinicopathological significance of protein disulphide isomerase A3 and phosphorylated signal transducer and activator of transcription 3 in cervical carcinoma.

Introduction: Death in cervical cancer patients is usually due to invasion and metastasis due to the aggressive nature of the tumour. Therefore, it is critical to identify potent therapeutic targets and prognostic markers to detect high-risk patients. Material and methods: We assessed the immunohistochemical expression of protein disulphide isomerase A3 (PDIA3) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in 50 cases of cervical carcinoma, and we investigated their association with clinicopathological characteristics. Results: High PDIA3 was detected in 50% of cases, and statistical analysis revealed a positive correlation between high PDAI3 expression and tumour grade (p < 0.001) and large tumour size (p = 0.010), depth of stromal invasion (p = 0.017), lymph-vascular invasion (p = 0.005), parametrial invasion (p < 0.001), nodal metastasis (p < 0.001), and higher International Federation of Gynaecology and Obstetrics stages (p < 0.001). Positive nuclear expression of p-STAT3 was detected in 44% of cases and showed significant association with histological grade (p = 0.036), tumour stage (p = 0.021), nodal metastasis (p = 0.020), and parametrial invasion (p = 0.045); statistical analysis of the patient's survival data revealed that shorter overall survival and disease-free survival, S, were associated with high PDIA3 expression and positive p-STAT3 immunoexpression. Conclusions: The high expression of PDIA3 and p-STAT3 was related to highly aggressive cervical carcinoma with poor prognosis, and high risk of recurrence after the standardised protocol of treatment. Hence, both PDIA3 and p-STAT3 could be considered as novel biomarkers for tumour progression and promising targets in the management of cervical carcinoma patients.

Predictive Value of Tumor-Infiltrating Lymphocytes and Ki-67 for Pathological Response to Total Neoadjuvant Therapy in Rectal Cancer.

PURPOSE: Patients with locally advanced rectal cancer (LARC) who underwent total neoadjuvant therapy (TNT) showed an increase in the percentage of complete pathological response (pCR). The purpose of this study was to determine the correlation between Ki-67, tumor-infiltrating lymphocytes (TIL), and TNT in LARC patients. METHOD: In total, one hundred fifty-nine patients with LARC were included in this prospective study. The international working group was used to categorize the TIL into three groups based on the percentage and density of staining: group 0 (0-10%), group 1 (11-59%), and group 2 (≥ 60%). Ki-67 expression was classified as low (≤ 50%) or high (> 50%). RESULT: Most patients had tumor grade III (74.2%) and T2-T3 (78.6%). Lymph node involvement (48.7%) and tumor size ≥ 3 cm were detected in approximately half of the patients. Forty-four percent of patients had a high Ki-67 index; 15.7% of patients belonged to group 1, and 21.4% belonged to group 2. pCR was detected in 18.2% of the patients. TIL and Ki-67 levels were significantly correlated with pCR (p = 0.001 and 0.003 for multivariate analysis and 0.001 and 0.03 for univariate analysis, respectively). CONCLUSION: There was a statistically significant correlation between Ki-67, TIL, and pCR following TNT protocol, which may help maximize the therapeutic outcome.

Immunohistochemical Expression of Immune Checkpoints; CTLA-4, LAG3, and TIM-3 in Cancer Cells and Tumor-infiltrating Lymphocytes (TILs) in Colorectal Carcinoma.

BACKGROUND: Colorectal cancer is considered the third most prevalent cancer in both sexes. Immune checkpoint receptors that regulate T-cell response, stimulation, and development include lymphocyte activating gene 3 (LAG-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (Tim-3). In addition, they are crucial for the advancement of cancer and tumor immune escape. OBJECTIVE: This work's aim was to assess the immunohistochemistry expression of Tim-3, CTLA-4, and LAG-3 in cancer cells and tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) and the correlation between these markers and clinicopathological variables and survival data. METHODS: This study involved 206 CRC specimens processed for CTLA-4, LAG3, and TIM-3 immunohistochemistry and correlated with the clinicopathological and survival parameters of the patients. RESULTS: High CTLA-4 epithelial expression was highly related to the old age group, large tumor size, low tumor-stroma ratio (TSR), high grade, advanced stage, the presence of distant metastasis (DM), perineural invasion (PNI), necrosis, lymphovascular invasion (LVI), relapse, mortality, overall survival (OS), and disease-free survival (DFS), while negative CTLA-4 TILs expression was highly linked with the presence of gross perforation, low TSR, high tumor budding (TB) score, high grade, advanced stage, the existence of lymph node (LN) metastasis, DM, necrosis, LVI, PNI, DFS, mortality, and OS. Positive LAG-3 TILs expression was highly correlated with large tumor size, gross perforation, low TSR, high TB score, high grade, advanced phase, the presence of LN, necrosis, LVI, PNI, relapse DFS, mortality, and OS. High Tim-3 epithelial expression was extremely linked with low TSR, advanced phase, the presence of LN, LVI, PNI, relapse, DFS, mortality, and OS, while positive Tim-3 TILs expression was related to gross perforation, low TSR, high TB score, advanced stage, the presence of LN, DM, necrosis, relapse, DFS, mortality, and OS. CONCLUSIONS: The patients' poor prognosis may be related to the immunohistochemistry expression of LAG-3, Tim-3, and CTLA-4 in CRC cancer tissue and TILs. Poor patient consequences can result from the CTLA-4, Tim-3, and LAG-3 co-expression, but CTLA-4 TILs' expression of these proteins may inhibit the growth of tumors.

Prognostic Impact of FSTL3, ADAM12, and FAT4 in Patients of Colon Cancer: Clinicopathologic Study.

There is a cellular crosstalk between Wnt/ß-catenin and Hippo/Yes-related protein 1 signaling paths in colon cancer (CC) which promotes EMT processes that mediate the metastatic progression of CC. We aimed to evaluate follistatin-like 3 (FSTL3), ADAM12, and FAT4 expressions in CC. A statistical analysis was done to establish how disease-free survival, overall survival (OS), and relapse all performed a prognostic role. High FSTL3 was detected in 68% of CC and significantly related to left-sided tumors ( P = 0.002) and the advanced tumor features, such as metastasis ( P = 0.010), pT ( P = 0.006), high grade ( P = 0.005), lymph node contribution ( P = 0.013), and advanced stage ( P = 0.003). Positive ADAM12 expression was observed in 60% and significantly related to left-sided tumors ( P = 0.001) and significantly common in high grade ( P = 0.028), lymph node involvement ( P < 0.001), and advanced stage ( P = 0.004). Low FAT4 expression was recognized in 76% and linked with the right-sided tumors ( P = 0.036). FAT4 expression was contrariwise linked with CC grade ( P < 0.001). Furthermore, FAT4 expression was inversely correlated with lymph node involvement ( P = 0.002), metastasis ( P = 0.046), and advanced stage ( P = 0.002). During the follow-up, 14 cases were relapsed and positively associated with high FSTL3 expression ( P = 0.001) and ADAM12 expression ( P < 0.001), but negatively linked with FAT4 expression ( P = 0.003). Shorter disease-free survival was substantially correlated with positive ADAM12, extreme FSTL3, and low FAT4 expression ( P < 0.001, P = 0.002, P = 0.003, consecutively). Moreover, Kaplan-Meier curves demonstrated a significant correlation between shorter OS with extreme FSTL3, positive ADAM12, and low FAT4 ( P = 0.004, <0.001, 0.019, consecutively). High FSTL3, positive ADAM12, and low FAT4 expression are unfavorable prognostic influences in CC that may be accountable for relapse and therapeutic resistance in CC.

High-risk human papillomavirus enhances the expression of COX-2 VEGF, EGFR, ProEx-C, and TERT proteins in human papillomavirus-related multiphenotypic sinonasal carcinoma through activation of PI3K/Akt, pRb, and TERT signalling pathways.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a new type of sinonasal tumour that frequently drops out of accurate diagnosis. Human papillomavirus related multiphenotypic sinonasal carcinoma was previously known as HPV-related sinonasal carcinoma with adenoid cystic characteristics, and it is connected to high-risk HPV (HR-HPV) strains whose prognosis is unknown. We aim to evaluate PI3K/Akt, pRb, and h telomerase reverse transcriptase (TERT) signalling pathway activation through the expression of proteins cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), ProEx-C, and TERT and their prognostic and clinicopathological value in HMSC patients. Sections of the 40 paraffin blocks of HMSC were recovered, and all samples were evaluated for the presence of a cocktail of HR-HPV, and the absence of MYB, NFIB, and MYBL1 fusions using fluorescence in situ hybridization; the presence of myoepithelial markers; S100, actin; the presence of squamous differentiation markers; calponin, p40, and p63 using PCR-based assays; and COX-2,VEGF, ProEx-C, and TERT using immunohistochemical staining. All patients were monitored for around 54 months, until death, or the last known surviving data (range 20-60 months). A statistically significant relationship exists between COX-2 expression was significantly related to the old age group, tumour extent, relapse, mortality, and poor DFS; (p = 0.001), (p = 0.01), (p = 0.002), and (p = 0.035), respectively. While VEGF, ProEx-C, and TERT expression with the old age group, tumour extent, lymph node metastasis, advancedstaging, relapse, mortality, poor disease free survival (DFS), and overall survival (p = 0.001). Human papillomavirus-related multiphenotypic sinonasal carcinoma is a unique sinonasal neoplasm with a strong link to HR-HPV strains. Expression of COX-2, VEGF, EGFR, ProEx-C, TERT was linked to poor prognosis, survival, and aggressive malignant behaviours such as proliferation, local recurrence, and lymph node metastasis, making them novel beneficial biomarkers and targeted therapies for HMSC patients.