scholarly journals MCM2 Expression in Different Molecular Subtypes of Epithelial Breast Cancers and its Association with Clinicopathological Parameters and Ki-67 Expression

Author(s):  
Meghadipa Mandal ◽  
Anadi Roy Chowdhury ◽  
Susmita Mukhopadhyay

Introduction: Breast cancer is one of the most common malignancies, with few subtypes having a more aggressive outcome and resistance to conventional therapies, Triple Negative Breast Cancers (TNBCs) being one such variant. The Ki-67 lacks reproducibility and a standardised cut-off. MCM2 (Minichromosome Maintenance 2) has role in DNA repair and replication and its role as alternate marker for prognosis has been studied in this case. Aim: To study MCM2 expression with respect to histologic grade, stage, nodal status and molecular subtypes of breast carcinoma. Also, to look for any correlation between Ki-67 and MCM2 expressions. Materials and Methods: A cross-sectional, observational study conducted on a group of 20 patients who underwent mastectomy in a Tertiary Care Centre, R.G. Kar Medical College and Hospital, Kolkata, West Bengal, India, for a total duration of six months. Histologic grading, staging, nodal status was evaluated from Haematoxylin and Eosin (H&E) stained sections. Formalin-Fixed Paraffin-Embedded (FFPE) blocks suitable for Immunohistochemistry (IHC) were selected and MCM2, Estrogen Receptor (ER), Human Epidermal Growth Factor Receptor 2 (HER2), Progesterone Receptor (PR)/neu and Ki-67 were performed. Scores given based on visual examination under light microscope. Analysis was done using IBM Statistical Package for the Social Sciences (SPSS) version 25.0 software. Results: Most of the subjects belonged to 41-55 years age group. Statistical significance was seen between high MCM2 and Ki- 67 expressions (p-value=0.0171) and high histologic grade and TNBCs (p-value=0.009). High MCM2 and Ki-67 expressions also come with increased risk for advanced disease. High Ki-67 is also a risk predictor for lymph node positive cases. Positive correlation was seen between MCM2 and (R)= 0.4318. Conclusion: The MCM2 is a predictor for adverse outcomes in breast carcinoma cases. It may serve as an alternative to Ki-67 as a proliferation marker, to guide clinicians in treatment strategies. Its role as a therapeutic target in aggressive breast carcinomas may be evaluated with larger study population in the future.

Biomedicine ◽  
2021 ◽  
Vol 41 (1) ◽  
pp. 75-81
Author(s):  
N. Priyathersini ◽  
J. Thanka ◽  
B Jayashree

Introduction and Aim: Breast cancer is the most common malignancy in females worldwide. Almost 1.4 million new cases have been diagnosed with breast cancer every year. This aims to study the clinicopathological profile and molecular subtypes of invasive breast carcinoma in resected mastectomy specimens over a period of 5 years. Materials and Methods:A retrospective study of 90 mastectomy and wide local resection specimens received during the period of January 2012 to June 2017 were analyzed. The clinical data of patients including age, gender, and stage of the diseasewere obtained from the medical records section. Immunohistochemical staining for Estrogen Receptor [ER], Progesterone Receptor[PR] and Human Epidermal Growth Factor Receptor 2HER2neu were done.The cases were classified according to the molecular classification based on the ER, PR and HER2 receptor status. Results: The peak incidence of breast carcinoma was in the age group 50 to 60 years. Invasive ductal carcinoma,Not otherwise specified[NOS] accounted for the most common histologic type. There was higher incidence of pT2 tumors in our study. The most common molecular subtype was luminal A, followed by triple negative tumors. These molecular subtypes associated well with Tumor grade and HGDCIS with a statistically significant p value of 0.001 and 0.015 respectively. An increased proportion of Grade 3 tumors were Triple Negative tumors. Conclusion:In breast carcinomas the routine histopathological features provide inexpensive method for understanding tumour biology and prognosis. It`s essential in areas with poor resources. ER, PR and HER2 assessment helps in identifying hormonal status and enables for hormone therapy and anti HER2 therapy.  


2021 ◽  
Vol 7 (2) ◽  
pp. 71-77
Author(s):  
Dr. Priyanka A ◽  
◽  
Dr. Muthu Sudalaimuthu ◽  
Dr. G. Shivashekar ◽  
◽  
...  

Context: Breast carcinoma is a heterogenous disease with varied clinicopathological features andresponse to therapy. Molecular classification through gene studies helps in planning therapy but haseconomic constraints. Hence immunohistochemical subtyping of breast carcinomas has been used asa surrogate method. Criteria for this subtyping has undergone many modifications since it wasoriginally proposed. Objectives: To immunohistochemically subtype breast carcinomas based onSt.Gallen 2017 guidelines and analyse the differences in clinicopathological parameters like age,tumour size, histopathological grade and lymph node staging between the various subtypes.Materials and methods: The study was done retrospectively at a tertiary care health centre inSouth India on breast carcinoma patients from January 2017 to June 2020. Immunohistochemistrywas done with antibodies to the Estrogen receptor, Progesterone receptor, Human epidermal growthfactor receptor-2 (HER-2) and Ki-67. Immunohistochemical Subtypes were correlated withClinicopathological features. Results: The study had 107 cases. Hormone receptor (HR) positiveHER-2 negative was the most common subtype (55 cases, 51.4%). This subtype frequentlypresented without nodal metastasis (58.2%) and in >50 years of age (56.4%). Triple-negativesubtype frequently presented with grade III (69.2%), highest nodal metastasis stage (38.5%) andin < 50 years of age (69.2%). Conclusion: St.Gallen 2017 guidelines for immunohistochemicalsubtyping classified breast carcinomas into groups that differed significantly in theirclinicopathological features. Further studies on differences in treatment response and survival ratedifferences between these different subtypes are needed.


Author(s):  
Nina Čamdžić ◽  
Suada Kuskunović-Vlahovljak ◽  
Svjetlana Radović ◽  
Mirsad Dorić ◽  
Mirsad Babić ◽  
...  

Introduction: Tumor microenvironment plays a significant role in tumor progression. Tumor stroma is one of the strongest modifiers of tumor cell response, cancer behavior, and cancer progression. This study aimed to investigate the correlation of matrix metalloproteinase-9 (MMP-9) expression and tumor-stroma ratio (TSR) with standard clinicopathological parameters in different molecular subtypes of breast cancer.Methods: Ninety biopsy samples of primary breast cancer diagnosed at the Department of Pathology, School of Medicine, Sarajevo, were selected for this study. The molecular subtype was determined based on the immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. Stromal and tumoral MMP-9 immunohistochemical expression and the TSR were determined for each tumor.Results: Tumoral MMP-9 expression correlated positively with the presence of lymphovascular invasion (p= 0.016). TSR showed significant association and correlation with tumor grade (G) (p= 0.031; p= 0.049) and tumor size (pT) (p = 0.049;p= 0.021, respectively). Stromal MMP-9 expression correlated with histologic type, histologic grade of tumor, and lymphocytic inflammatory infiltrate (p= 0.021;p= 0.047, p= 0.038, respectively). A higher percentage of stromal MMP-9 expression correlated with the strongest lymphocytic response (p = 0.007). Significant correlation was observed between molecular subtypes and histologic grade of the tumor (p= 0.032).Conclusion: Our results, to some extent, confirm the significance of the tumor microenvironment in breast cancer, especially when it is about stromal MMP-9 expression. Although we observed significant association, without linear correlation, we found no significant correlation between molecular subtypes of breast cancer and MMP-9 expression.


2020 ◽  
Author(s):  
Dr. Animesh Ray ◽  
Dr. Komal Singh ◽  
Souvick Chattopadhyay ◽  
Farha Mehdi ◽  
Dr. Gaurav Batra ◽  
...  

BACKGROUND Seroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate the true extent of infection in a population. However, seroprevalence studies have been scarce in South East Asia including India, which, as of now, carries the third largest burden of confirmed cases in the world. The present study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among hospitalized patients at one of the largest government hospital in India OBJECTIVE The primary objective of this study is to estimate the seroprevalence of SARS-CoV-2 antibody among patients admitted to the Medicine ward and ICU METHODS This cross-sectional study, conducted at a tertiary care hospital in North India, recruited consecutive patients who were negative for SARS-CoV-2 by RT-PCR or CB-NAAT. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method RESULTS A total of 212 hospitalized patients were recruited in the study with mean age (±SD) of 41.2 (±15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 19.8%patients(95% CI 14.7-25.8). Residency in Delhi conferred a higher frequency of seropositivity 26.5% (95% CI 19.3-34.7) as compared to that of other states 8% (95% CI 3.0-16.4) with p-value 0.001. No particular age groups or socio-economic strata showed a higher proportion of seropositivity CONCLUSIONS Around, one-fifth of hospitalized patients, who were not diagnosed with COVID-19 before, demonstrated seropositivity against SARS-CoV-2. While there was no significant difference in the different age groups and socio-economic classes; residence in Delhi was associated with increased risk (relative risk of 3.62, 95% CI 1.59-8.21)


2014 ◽  
Vol 29 (1) ◽  
pp. e1-e7 ◽  
Author(s):  
Yanzhi Zhang ◽  
Peng Wang ◽  
Mumu Shi ◽  
Hironobu Sasano ◽  
Monica S.M. Chan ◽  
...  

Background Disparities of biomarkers’ expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. Methods The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. Results The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Conclusion Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.


2016 ◽  
Vol 70 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Carla Thomas ◽  
Cleo Robinson ◽  
Ben Dessauvagie ◽  
Benjamin Wood ◽  
Greg Sterrett ◽  
...  

AimBreast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.MethodsExpression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.ResultsExpression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).ConclusionsThis study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.


2021 ◽  
pp. 144-149
Author(s):  
K. Indumathi ◽  
E. Theranirajan ◽  
G. Bhavani

BACKGROUND: This is a retrospective study of 60 cases, to detect the expression of ER, PR, HER2neu, CK5/6 and Ki67 proliferation index in breast carcinomas by immunohistochemical method and to determine the newer molecular classication. Few patients have recurrence inspite of being diagnosed under the category of low risk and few do well in the high risk group which can be attributed to the molecular level differentiation. AIM: The aim of this study is to categorize the patients under molecular classication, and to compare the clinicopathological parameters with it and to denote the signicance of targeted therapy. MATERIALS AND METHODS: A retrospective study of detecting the expression of the above said markers in modied radical mastectomy specimens received at a tertiary care centre during the period from January 2015 to June 2018. A total of 60 cases which included 30 of IDC NST and 30 cases of special variants were selected for immunohistochemical analysis. RESULTS: Out of the 60 cases studied, the most common was found to be the luminal A type comprising 37% and the least common was the luminal B and hybrid types each comprising 8%. The most common grade for HER2 was Grade III (50%). The association of histological grade with the molecular classication was statistically signicant with the p value of 0.01. Basal type (56%) had the highest incidence of N3 stage. ER, PR, HER2 neu, CK5/6 expression and proliferation index with Ki67 had a statistically signicant association with the molecular classication. High proliferation index (>14%) with Ki67 was noted in Luminal B, Basal and Hybrid types. 78% of the total 60 cases were alive and healthy. One death was reported in HER2, Hybrid and Basal types. The negative kappa value obtained while studying the agreement between the histopathological and molecular classication, indicates that the agreement is worse than chance and hence the importance of molecular classication is substantiated for the targeted therapy.


Author(s):  
Devi Meenakshi K. ◽  
Arasar Seeralar A. T. ◽  
Srinivasan Padmanaban

Background: Very low birth weight (VLBW) babies are at increased risk of a number of complications both immediate and late. Worldwide it has been observed that these babies contribute to a significant extent to neonatal mortality and morbidity. Aim of the study was to study the risk factors contributing to mortality in VLBW babies and to evaluate the morbidity pattern in these infants.Methods: A retrospective analysis of data retrieved from the case records of VLBW babies admitted in the NICU of Kilpauk Medical College between January 2015 to December 2015. Out of the 2360 intramural babies admitted during the study period, 99 babies were less than 1500 gms. The risk factors for these babies were analyzed for their association with the outcome. Data were statistically analyzed.Results: In present study, we found that sex of the baby, gestational age, obstetric score, birth asphyxia, pulmonary haemorrhage, ROP and presence of shock were found to be associated with increased mortality. By logistic regression analysis it was observed that birth weight of the baby (p value 0.002), duration of stay (p value 0.0006), presence of shock (p<0.0001), were the risk factors significantly associated with poor outcome.Conclusions: Among the maternal and neonatal factors analyzed in the study using logistic regression analysis, birth weight, duration of hospital stay and presence of shock were significantly related to poor outcome. Of these presence of shock was the single most important factor that predicted increased mortality.


Author(s):  
Rituparna Ghosh ◽  
Sarojini Raman ◽  
Jayasree Rath

Introduction: Colorectal Cancer (CRC) is third most common malignancy worldwide. Various genomic alterations play fundamental role in initiation and progression of CRC. Among these, p53 mutation has a crucial role in survival and metastasis and its point mutation induces Vascular Endothelial Growth Factor (VEGF) promoting vascular permeability, migration and differentiation. The degree of angiogenesis can be measured by Microvascular Density (MVD) using CD34, which is helpful in identifying high risk patients for recurrence and metastasis. Aim: The aim of the study was to analyse the expression of p53, VEGF and MVD in CRC and their association with clinicopathological parameters. Materials and Methods: The ambispective study of 2 year duration was conducted from September 2015 to July 2017 in the Department of Pathology, Kalinga Institute of Medical Sciences and PBMH, Bhubaneswar. It included CRC resection specimens and archival tissue blocks. Tissue microarray blocks were prepared manually for IHC application in total 70 cases (58 (82.9%) adenocarcinomas and 12 (17.1%) adenomas) which were histologically staged and graded as per American Joint Committee on Cancer (AJCC) and World Health Organisation (WHO) guidelines. Pearson chi-square test and fisher’s-exact method were used to find significance of p53, VEGF and CD34 expression in adenomas and adenocarcinomas with respect to clinicopathological parameters. Results: No significant statistical association was found between p53, VEGF and MVD with tumour grade and nodal status. Majority, 41 (70.69%) cases were hypervascular (MVD-High). Adenomas 9 (75%) cases, were mostly hypovascular (MVD-Low) with p-value of 0.003. There was significant statistical association between VEGF and MVD with a p-value of 0.01. VEGF and MVD were more expressed on left-sided colon cancers. There was significant statistical association (p=0.01) between p53 graded expression and diagnosis in the present study. MVD and tumour nodal status had an inversely significant relationship (p=0.03). Conclusion: p53 and VEGF expressed more on carcinomas than adenomas. Both p53 and VEGF induce angiogenesis which can be effectively measured by CD34 expression (MVD). There is a directly proportional relationship of angiogenesis and malignant transformation. So these three IHC markers together can be considered a significant prognostic factor involved in CRC.


Author(s):  
Vasudeva Acharya ◽  
Mohammed Fahad Khan ◽  
Srinivas Kosuru ◽  
Sneha Mallya

Background: Dengue is one of the important causes of acute febrile illnesses in India. Dengue can be a fatal disease, however there are no reliable markers which can predict mortality among these patients.Methods: A prospective cross sectional study was done in patients who were admitted to a tertiary care hospital with features of dengue fever. A total of 364 patients with IgM dengue serology positive were included in the study. Relevant clinical and laboratory parameters were collected from all patients. Association between clinico-laboratory parameters with mortality was studied using appropriate statistical methods.Results: Among the 364 patients recruited in this study, 14 (3.85%) patients died. Mortality among patients with age group 18-40 years was 2.04%, in patients aged above 40 years was 7.56%. Mortality among patients with hypotension was 42.42% (14 out of 33), bleeding manifestations was 15.38% (8/52), platelets <20,000/mm3 was 10.41% (10/96), ALT >200 was 13.04% (6/46), AST>200 was 12.34% (10/81), prolonged prothrombin time was 60%(12/20), renal failure was 28%(14/50), encephalopathy was 31.57% (6/19), multi organ dysfunction syndrome(MODS) was 43.33% (13/30), acute respiratory distress syndrome (ARDS) was 45.45% (5/11), pleural effusion was 7.5% (6/80).Conclusions: The overall mortality in the present study was 3.85%. Following variables were associated with increased risk of death among the dengue patients: Age >40 years, presence of hypotension, platelets <20000 cells/mm3, ALT>200U/L, AST>200U/L, prolonged prothrombin time, presence of renal failure, encephalopathy, MODS, ARDS and bleeding tendency (p value <0.05). Early identification of factors associated with mortality can help to make appropriate decision on care required.


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