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ASSESSMENT OF TUMOUR PROLIFERATION BY USE OF THE MITOTIC ACTIVITY INDEX, Ki67 AND PHOSPHOHISTONE H3 EXPRESSION IN INFILTRATING DUCTAL CARCINOMA OF BREAST

2024-07-01T00:00:00Z

Title: ASSESSMENT OF TUMOUR PROLIFERATION BY USE OF THE MITOTIC ACTIVITY INDEX, Ki67 AND PHOSPHOHISTONE H3 EXPRESSION IN INFILTRATING DUCTAL CARCINOMA OF BREAST Authors: ZUBIYA SUHA FATHIMA Abstract: Background Infiltrating ductal carcinoma (IDC) of the breast is a common and aggressive form of breast cancer. Traditional histopathological methods using MAI- Hematoxylin and Eosin (H&E) staining have limitations in accurately assessing tumor proliferation. Immunohistochemical markers like Ki67 and phosphohistone H3 (PHH3) provide enhanced insights into tumor biology and prognostic evaluation. AIMS To assess PHH3 and Ki67 expression in infiltrating ductal carcinoma of the breast and correlate it with mitotic activity index. Additionally, to investigate their association with histological grade and staging of the carcinoma. OBJECTIVES 1. To determine the expression of PHH3 and Ki67 in infiltrating ductal carcinoma breast 2. To correlate mitotic activity index with the expression of PHH3 and Ki67 in infiltrating ductal carcinoma breast 3. To study the association between mitotic activity index, Ki67 and phosphohistone H3 expression with Histological grade and staging of ductal carcinoma breast. Methods A cross-sectional observational study was conducted in the Department of Pathology, Sri Devaraj Urs Medical College, from July 2019 to June 2023. The study included 102 histologically confirmed cases of IDC. Immunohistochemical staining for PHH3 and Ki67 was performed on tumor sections, and the results were compared with H&E staining. Statistical analysis was conducted using SPSS software. xxv Results The majority of the cases (56.9%) were individuals above 50 years of age, with a mean age of 51.46 years. Tumor sizes were predominantly less than 5 cm in 55.9% of the cases, and 52% were at T2 stage. Lymph node involvement was observed in 53.92% of cases, and lymphovascular invasion was present in 34.3%. Tumor-infiltrating lymphocytes (TILs) were mostly below 10% in 66.7% of cases. PHH3 staining identified higher mitotic activity compared to H&E, leading to significant upgrades in mitotic scores and Modified Bloom-Richardson (mBR) grades. Ki67 expression showed a significant correlation with lymph node involvement but not with disease stage. Conclusions PHH3 staining demonstrated superior sensitivity in detecting mitotic figures and provided more accurate grading and prognostic information compared to H&E staining. Ki67 expression was significantly associated with lymph node involvement, highlighting its prognostic value. The findings support the integration of PHH3 staining in routine diagnostic practices to improve the accuracy of breast cancer grading and prognosis.

IMMUNOHISTOCHEMICAL EXPRESSION E-CADHERIN IN THE BASEMENT MEMBRANE OF CYTOTROPHOBLAST, SYNCYTIOTROPHOBLAST AND BLOOD VESSELS OF PLACENTA OF PRE-ECLAMPSIA

2024-07-01T00:00:00Z

Title: IMMUNOHISTOCHEMICAL EXPRESSION E-CADHERIN IN THE BASEMENT MEMBRANE OF CYTOTROPHOBLAST, SYNCYTIOTROPHOBLAST AND BLOOD VESSELS OF PLACENTA OF PRE-ECLAMPSIA Authors: SUKKA SAHITI Abstract: BACKGROUND: Pre-eclampsia, a severe pregnancy condition which is evident by increased blood pressure and proteinuria after 20 weeks. Affecting 2-5% of all the pregnancies globally, it carries significant risks for both mother and baby.1 During pregnancy in the initial months there is a temporary decrease in E-cadherin expression within trophoblastic cells as they invade placenta, nevertheless the function of E-cadherin in regulation of placental vascularity is not fully understood. Hence this study aims to analyse the intensity and distribution of E-cadherin staining within the trophoblastic villi in healthy and pre-eclampsia placenta patients. AIMS & OBJECTIVES: 1. To determine the Immunohistochemistry (IHC) expression of E-cadherin in the placenta of healthy normal pregnancy and the placenta of pre-eclampsia. 2. To study the correlation of intensity of expression of E-cadherin and the severity of pre-eclampsia. MATERIALS & METHODS: This study was performed in Department of Pathology in association with Department of Obstetrics & Gynaecology, Sri Devaraj Urs Medical College attached to RLJH and Research Center, Tamaka, Kolar during the period of September 2022 to December 2023. The study included a total of 160 placenta cases that included 80 pre-eclampsia placentas and 80 normal healthy controls. IHC was performed using antibodies against E-cadherin and expression of E-cadherin was analysed and interpreted. E-cadherin expression was compared among the cases and the controls and was also correlated with clinicopathological parameters. Statistical xx analysis was performed using Chi-square test and mean along with standard deviation was also calculated. A p value of <0.05 was considered significant. RESULTS: The average median age of cases and controls was 26 years. Not only the age of females but also gestational age of the pregnant women along with gross weight of placenta, weight of baby, apgar score of the baby all these clinicopathological parameters were correlated among the pre-eclampsia cases and the healthy pregnant controls. The gross and microscopic findings that is necrosis, calcification, and thrombosis when compared among the preeclampsia cases and the healthy controls, these findings were more evident in the preeclampsia placentas compared to normal healthy controls and were statistically significant. The immunohistochemical expression of e-cadherin was measured in both healthy controls and pre-eclampsia cases and it showed high (grade 3) and continuity of expression e-cadherin in majority of the normal healthy placental villi and there was predominantly varied expression (grade 0,1,2&3) along with discontinuity in the staining of the placental villi in pre-eclamptic placentas and these findings were statistically significant. CONCLUSION: This study indicates that the reduced intensity and discontinuity of E-cadherin staining in preeclampsia cases point to a defect in placental barrier function. This defect likely contributes to the development of pre-eclampsia and associated pregnancy complications.

PROGRAMMED DEATH LIGAND-1 AND MUTL HOMOLOG-1 EXPRESSION IN COLORECTAL CANCER AND ITS CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS

2024-07-01T00:00:00Z

Title: PROGRAMMED DEATH LIGAND-1 AND MUTL HOMOLOG-1 EXPRESSION IN COLORECTAL CANCER AND ITS CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS Authors: QUEEN MARY, A Abstract: Background: Programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) has garnered significant attention due to its implications for immunotherapy and patient prognosis. PD-L1, a transmembrane protein, performs a crucial part in the immune system’s ability to regulate the balance between T cell activation and tolerance. In the context of CRC, PD-L1 expression can result in the inhibition of anti-tumor immune responses, allowing cancer cells to evade immune surveillance. Microsatellite instability (MSI) is a state defined by the accumulation of brief mutations; repetitive DNA sequences known as microsatellites. This condition results from defects in the DNA mismatch repair (MMR) system, which normally corrects errors that occur during DNA replication. MSI is a hallmark of a subset of CRCs and is connected to distinct clinical and pathological features, including a better response to certain immunotherapies. Aim of the study: 1. To determine the expression of Programmed Death Ligand-1(PD-L1) in colorectal carcinomas. 2. To determine the expression of MutL Homolog-1 (MLH-1) for Microsatellite instability status in colorectal carcinomas. 3. To determine the association of PD- L1 and MLH-1 expression with clinic pathological parameters of colorectal carcinoma. Materials and Methods: The study was conducted in Department of Pathology in Collaboration with Department of General Surgery, Sri Devaraj Urs Medical College attached to RL Jalappa Hospital and Research centre, Tamaka, Kolar during the period of August 2022 to May 2024. The study includes 76 cases of colorectal carcinoma diagnosed by histopathology. IHC was performed using the antibodies against PDL1. Expression of PDL1 was documented and analysed. Statistical analysis was performed using Chi-square test or Fischers exact test. A p value of less than 0.005 was considered statistically significant. Results: Peak incidence was seen in the 60-69 years age group (38.2%). Most frequent side of tumor was on the Left side (75%). Majority of the cases showed Moderate differentiated Adenocarcinoma (51.3%) and majority of the patients were belonging to T3 stage of the tumor 25 xxv (53%). TNM Stage II (28%) had more cases followed by TNM Stage II (28%). TILs was graded according to ITWG Methodology: The percentage of TILs was categorized into 3 groups: low (0-10%), intermediate (15-50%) and high (55-100%). Majority of the cases were of Low TILs (52.6%). Most of the cases for Tumor stroma ratio in colorectal cancer were of ≤50% (61.8%). 20.3% showed PDL1 expression and 44.8% showed MLH 1 expression. PDL1, MLH1 and TSR showed significant association with TILs. Significant association was noted between PDL1 and TILs with a p value of 0.012. MLH1 also showed significant association with TILs with a p value of 0.041. On comparing TILs and TSR the p value was 0.001 which was statistically significant. Conclusion: Study of 76 cases of Colorectal cancer showed PDL1 expression in 20.3% and MLH 1 expression in 44.8% cases. PDL1 and MLH1 showed a significant association on comparing with TILs in colorectal carcinoma. Also MLH1 showed significant association with TNM staging. Study of PDL1 and MLH1 helps in prognostification and management of Colorectal carcinoma.

EXPRESSION OF CLASPIN IN SQUAMOUS CELL CARCINOMA OF CERVIX AND ITS ASSOCIATION WITH P16 EXPRESSION AND CLINICOPATHOLOGIC PARAMETERS

2024-07-01T00:00:00Z

Title: EXPRESSION OF CLASPIN IN SQUAMOUS CELL CARCINOMA OF CERVIX AND ITS ASSOCIATION WITH P16 EXPRESSION AND CLINICOPATHOLOGIC PARAMETERS Authors: HANEENA MARIYAM KUKKAMGAI Abstract: Background: Cervical cancer is a preventable gynecological malignancy, yet it remains a significant health burden in developing countries. While screening and vaccination must be our primary objective to fight against cervical cancer, the ground reality that the diagnosis is still made most frequently at an advanced stage cannot be forgotten. Hence biomarkers identified in cervical cancer has significance in understanding the prognosis and reducing cervical cancer related deaths. Claspin is a protein with key role in checkpoint signaling, genome duplication and consecutively increased replication. Elevated levels of Claspin have been seen in multiple solid tumors. Aim of the study: To associate of Claspin expression with clinicopathological parameters and P16 expression in Squamous Cell Carcinoma (SCC) of Cervix. Methods: The study was conducted in Department of Pathology in Collaboration with Department of Obstetrics and Gynecology (OBG), Sri Devaraj Urs Medical College attached to R.L.Jalappa Hospital and Research center, Tamaka, Kolar during the period of July 2022 to December 2023.The study included 80 cases of primary diagnosis of SCC cervix along with 10 cases of High grade squamous intraepithelial lesion (HSIL) and 10 cases of cervical tissue with normal histological features. Immunohistochemistry (IHC) was performed using antibodies against P16 and Claspin. Expression of Claspin and P16 was analyzed and interpreted. Claspin expression was associated with P16 and xvi clinicopathological parameters of carcinoma cervix. Statistical analysis was performed using Chi-square test. A p value of less than 0.05 was considered substantially significant. Results: The average age of cervical carcinoma diagnosis in this study was 55 years, with a significant majority (73.75%) being post-menopausal. All of the subjects had symptomatic presentation, most commonly bleeding per vagina (52.5%) and on per speculum examination 70% cases had an ulceroproliferative growth. On radiological examination majority of the cases had tumor size more than 4cm (68.5%) but lymph node involvement was seen in only (31.5%) cases. Maximum number of cases were diagnosed in Stage III highlighting the late presentation of the rural population in India. On histopathological examination most cases were well- differentiated (63.75%) and TILs were seen markedly increased in 56.92% cases. The study also found block positivity for P16 in 83.75% of cases, indicating HPV-associated SCC. Claspin is a potential biomarker, highly expressed in SCC cervix (88.75%, p<0.005), significantly higher than HSIL (50%) and normal tissue (0%). Increased Claspin expression was linked to P16 positivity but was not statistically significant. Neither Claspin nor P16 showed any significant association with the various clinicopathological parameters such as age, postmenopausal status, parity, clinical findings, lymph node status, size of tumor, stage, grade and TILs. Conclusion: Claspin is a potential biomarker for cervical cancer, particularly in HPV-associated cases. This study has shown the increased expression of Claspin and P16 in cervical cancer. xvii Drugs targeting Claspin has the potential to increase sensitivity to chemotherapeutic drugs like Cisplatin. Further research is needed to explore its prognostic significance and relationship with clinicopathological parameters. This study contributes to the ongoing quest for effective biomarkers, ultimately aiming to improve patient outcomes and reduce mortality rates in cervical cancer.