Study of Comparison of Magnetic Resonance Imaging with Surgical and Pathological features in Carcinoma Rectum Patients.

Colorectal cancer is the second-most common cancer in the females and third-most common cancer in males worldwide and it is the second-most common cause of mortality. In India, colorectal cancer is the fifth-most common cancer overall, constituting 6.3%. With the advent of high-resolution magnetic resonance imaging (MRI), it has become the investigation of choice for local staging of rectal cancers as well as in predicting the response to neoadjuvant treatment and streamlining the management. The aims and objectives of this study were to compare the results of MRI with surgicopathological findings in carcinoma (Ca) rectum patients in Indian patients from a tertiary regional Cancer care centre. An observational retrospective study was carried out in the Department of Surgical Oncology Acharya Harihar Regional Cancer Centre, Cuttack, from January 2021 to June 2022. All the patients who were admitted and planned for the definitive surgery for Ca Rectum and Recto sigmoid Ca were included in the study. A total of 68 patients were included, including both upfront and post-neoadjuvant treatment cases. All the patients who received neoadjuvant treatment underwent an MRI for local staging. The findings of MRI were compared with surgical and histopathology results. Results were compared in terms of T staging, N staging and response to neoadjuvant therapy among MRI and surgical and pathological findings. Overall, there was good agreement between MRI and operative findings and histopathological findings.

Evaluation of micrometastasis and isolated tumor cells in node-negative early-stage oral tongue squamous cell carcinoma: a cross-sectional study in tertiary-level hospitals in eastern India.

OBJECTIVE: The present study aimed to investigate the incidence of micrometastasis (MMs) and isolated tumor cells (ITCs) in node-negative early-stage oral tongue squamous cell carcinoma (T1-T2 N0). The secondary objective was to correlate the incidence with the clinicopathologic parameters of age, sex, depth of invasion, pattern of invasion, host lymphocytic response, and size and grade of primary tumor. STUDY DESIGN: Micrometastasis and ITCs in cervical nodes of 30 patients with early-stage oral tongue squamous cell carcinoma were detected and compared using 3 methods: routine hematoxylin and eosin staining, serial-sectioning at intervals of 150 microns employing hematoxylin and eosin, and serial sectioning pan-cytokeratin immunostaining. Associations with clinicopathological variables were analyzed. RESULTS: Metastatic tumor cells were detected in the cervical nodes of 2 patients using serial sectioning and immunohistochemistry, resulting in upstaging of 6.6% of all cases. Level I and II lymph nodes were primarily involved. CONCLUSIONS: Early-stage oral tongue squamous cell carcinoma has a significant potential for MMs that frequently go undetected in routine histopathologic examination. However, laborious and technique-sensitive, serial sectioning in combination with pan-cytokeratin staining (AE1/AE3) may aid in detecting MMs and ITCs in patients with early-stage OTSCC.

Gallbladder cancer-associated genetic variants rs1003349 and rs1004030 regulate MMP14 expression by altering SOX10- and MYB-binding sites.

The pathogenesis of gallbladder cancer is complex, involving environmental and genetic risk factors. The matrix metallopeptidase 14 (MMP14) alters the tumor microenvironment and promotes tumorigenesis. In this study, we have characterized the role of the MMP14 promoter variants rs1004030 and rs1003049 in gallbladder cancer pathogenesis. Previously, we have shown the association of rs1004030 and rs1003049 with GBC and allele-specific differential expression of MMP14 in GBC patients. These variants reside within the cis-regulatory element (CRE) with high DNase and H3K4me3 signals, suggesting an active regulatory role in MMP14 expression. The luciferase-based reporter assay showed the role of promoter variants on expression levels in two GBC cell lines. Deleting the 119 bp promoter region surrounding the variants rs1004030 and rs1003049 by CRISPR-Cas9 genome editing resulted in reduced MMP14 expression in G415 cells. Electrophoretic mobility shift assay shows the presence of risk allele 'C'/'G' at rs1004030 and rs1003049 and create binding sites for transcription factors SOX10 and MYB, respectively. Further, stable knockdown of these transcription factors in G415 and TGBC1TKB cells showed reduced expression of MMP14. However, in both GBC cells, ectopic expression of these transcription factors increased the expression of MMP14. Rescue of MYB and SOX10 expression levels showed a significant increase in luciferase activity only in risk allele-carrying constructs. In conclusion, our study unveils a mechanistic role of the MMP14 promoter variants rs1004030 and rs1003049 in gallbladder cancer.

The profile of expression of the scaffold protein SG2NA(s) differs between cancer types and its interactome in normal vis-a-vis breast tumor tissues suggests its wide roles in regulating multiple cellular pathways.

Striatin and SG2NA are scaffold proteins that form signaling complexes called STRIPAK. It has been associated with developmental abnormalities, cancer, and several other diseases. Our earlier studies have shown that SG2NA forms a complex with the cancer-associated protein DJ-1 and the signaling kinase Akt, promoting cancer cell survival. In the present study, we used bioinformatics analyses to confirm the existence of two isoforms of human SG2NA, i.e., 78 and 87 kDas. In addition, several smaller isoforms like 35 kDa were also seen in western blot analyses of human cell lysates. The expression of these isoforms varies between different cancer cell lines of human origin. Also, the protein levels do not corroborate with its transcript levels, suggesting a complex regulation of its expression. In breast tumor tissues, the expression of the 35 and 78 kDa isoforms was higher as compared to the adjacent normal tissues, while the 87 kDa isoform was found in the breast tumor tissues only. With the progression of stages of breast cancer, while the expression of 78 kDa isoform decreased, 87 kDa became undetectable. In co-immunoprecipitation assays, the profile of the SG2NA interactome in breast tumors vis-à-vis adjacent normal breast tissues showed hundreds of common proteins. Also, some proteins were interacted with SG2NA in breast tumor tissues only. We conclude that SG2NA is involved in diverse cellular pathways and has roles in cellular reprogramming during tumorigenesis of the breast.

Genetic association of MMP14 promoter variants and their functional significance in gallbladder cancer pathogenesis.

Gallbladder cancer (GBC) is relatively rare but shows high frequency in certain geographical regions and ethnic groups, which include Northern and Eastern states of India. Previous studies in India have indicated the possible role of genetic predisposition in GBC pathogenesis. Although matrix metalloproteinase-14 (MMP14) is known modulator of tumour microenvironment and tumorigenesis and TCGA data also suggests its upregulation yet, its role in genetic predisposition for GBC is completely unknown. We explored MMP14 promoter genetic variants as risk factors and their implication in expression modulation and the pathogenesis of GBC. We genotyped all single nucleotide polymorphisms of MMP14 promoter by Sanger's sequencing in approximately 300 GBC and 300 control study subjects of Indian ethnicity and, in 26 GBC tissue samples. Protein expression of MMP14 in GBC tissue samples was checked by immunohistochemistry. In vitro luciferase reporter assay was carried out to elucidate role of promoter genetic variants on expression levels in two different cell lines. MMP14 promoter variants, rs1003349 (p value = 0.0008) and rs1004030 (p value = 0.0001) were significantly associated with GBC. Luciferase reporter assay showed high expression for risk alleles of both the SNPs. Genotype-phenotype correlation for rs1003349 and rs1004030, in patient sample, confirmed that risk allele carriers had higher expression levels of MMP14; moreover, the correlation pattern matched with genetic association models. Overall, this study unravels the association of MMP14 promoter SNPs with GBC which contribute to pathogenesis by increasing its expression.

Clinicopathological study of malignant melanoma in a regional cancer center.

BACKGROUND: : Malignant melanoma is a tumor of melanocytic origin. Although uncommon in India as compared with the west, its prevalence is increasing. OBJECTIVES: To document the pattern of clinicopathological features of malignant melanoma cases attending in a regional cancer center in eastern India. MATERIAL AND METHODS: The present study was a retrospective study of 182 cases diagnosed histopathologically as malignant melanoma during 2011-2016. RESULTS: Out of the total cases, 170 (93.4%) were cutaneous and 12 (6.6%) were noncutaneous melanoma. The most common age group was sixth decade with a male predominance. Conventional melanotic melanomas were 176 (96.70%), and only 6 cases (3.30%) were amelanotic melanoma. Among noncutaneous melanomas, 6 were in anorectum, 2 in conjunctiva, and 1 case each in nasal cavity, palate, gingivo-buccal sulcus, and vagina. The acrallentigenous type was the most common variety, and the mixed epithelioid and spindle cell type was the most common histopathological pattern. Clark's level III was the most common level of invasion. CONCLUSION: The lower extremity is the most common site for melanoma, whereas extracutaneous melanomas are exceedingly rare and aggressive neoplasms. Melanoma can metastasize to regional lymph nodes, however, visceral metastasis to liver can also occur. In the absence of pigment in amelanotic melanoma, immunohistochemical markers such as HMB 45 can be used for definitive diagnosis.