scholarly journals Evaluation of PTEN and Ki67 Expression in Typical and Atypical Endometriosis and Endometriosis Associated Ovarian Cancer

2020 ◽  
Vol 21 (11) ◽  
Author(s):  
Mojgan Akbarzadeh-Jahromi ◽  
Zahra Zare ◽  
Fatemeh Sari Aslani ◽  
Simin Torabinezhad

Background: Several studies reported that endometriosis is associated with an increased risk of ovarian cancer. Atypical endometriosis is common in patients with endometriosis-associated ovarian, which might be considered as a precancerous lesion. Objectives: This study aimed to assess ki67 and PTEN expression in endometriosis associated ovarian cancer (EAOC), atypical endometriosis, and typical endometriosis. Methods: In this study, all H & E slides of 260 ovarian endometriosis cases were reviewed. And 25 cases were diagnosed with atypical endometriosis. Forty-one typical endometrioses and 24 ovarian cancers with endometriosis were included. We assessed PTEN and Ki67 immunoexpression in epithelial and stromal cells. Results: The prevalence of atypical endometriosis was about 9%. PTEN loss was found in 12 (out of 24 or 50%) of EAOC, 2 (out of 25; 8%) of atypical endometriosis, and none of the typical endometriosis. In all 12 PTEN loss cases, the PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. A total of 7.3% of typical endometriosis and 8% atypical endometriosis and 33.3% of EAOC had Ki67 staining in more than 50% of the epithelial component. Both typical and atypical endometriosis showed similar PTEN loss and Ki 67 staining (in more than 50% of the epithelial component) (P value > 0.05), and both of them were different from EAOC (P value < 0.05). Conclusions: The PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. The result indicated that PTEN loss could be an early event in the tumor development pathway from endometriosis to ovarian cancer.

2019 ◽  
Author(s):  
Oana A. Zeleznik ◽  
Clary B. Clish ◽  
Peter Kraft ◽  
Julian Avila-Pancheco ◽  
A. Heather Eliassen ◽  
...  

AbstractBackgroundExperimental evidence supports a role of lipid dysregulation in ovarian cancer progression and metastasis. We estimated associations with ovarian cancer risk for circulating levels of four lipid groups measured 3-23 years before diagnosis.MethodsAnalyses were conducted among cases (N = 252) and matched controls (N = 252) from the Nurses’ Health Studies. We used logistic regression adjusting for risk factors to investigate associations of lysophosphatidylcholines (LPC), phosphatidylcholines (PC), ceramides (CER), and sphingomyelins (SM) with ovarian cancer risk overall and by histotype. A Bonferroni adjusted p-value threshold of 0.0125 (0.05/4; 4 measured lipid groups) was used to evaluate statistical significance. Odds ratios (OR; 10thto the 90thpercentile) and 95% confidence intervals of ovarian cancer risk were estimated.ResultsC16:0 SM, C18:0 SM, C16:0 CER and SM sum were significantly positively associated with ovarian cancer risk, with ORs ranging from 1.95-2.10, with stronger ORs for postmenopausal women (2.02-3.22). ORs were generally similar for serous/poorly differentiated and endometrioid/clear cell tumors, although most did not meet the Bonferroni-adjusted p-value for significance. C18:1 LPC and the ratio of LPC to PC were significantly inversely, while C18:0 SM was significantly positively, associated with risk of endometrioid/clear cell tumors.ConclusionElevated levels of circulating SMs 3-23 years before diagnosis were associated with increased risk of ovarian cancer, regardless of histotype, with stronger associations among postmenopausal women. Prospective and experimental studies are required to validate our findings and understand the role of lipid dysregulation, SMs in particular, in ovarian carcinogenesis.


2021 ◽  
Author(s):  
Binkai Yang ◽  
Yuanjing Hu ◽  
Tian Wang ◽  
Na Li ◽  
Wenwen Zhang

Abstract Objective: Our objective was to investigate the upregulated expression of ribonucleotide reductase M2 (RRM2) in the ectopic endometrium (EC) of ovarian endometriosis (OE) patients that may indicate malignant transformation. RRM2 may be used as a marker of OE, which contribute to the research of the mechanism of the malignant transformation of OE.Methods: The gene expression profiles of ovarian cancer and OE were downloaded from Gene Expression Omnibus (GEO), and a common hub gene, RRM2, was identified. The expression of RRM2 was low in OE and high in ovarian cancer. A total of 44 patients with endometriosis-associated ovarian cancers (EAOC) and 44 with OE were enrolled in this study. Immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of RRM2, while the relationship between RRM2 and Ki-67 was analyzed by IHC co-localization. Results: There was no significant difference in the expression of RRM2 in the eutopic endometrium (EU), EC, and cancer tissues of EAOC patients. Compared with OE patients, the mRNA and protein expression levels of RRM2 were higher in the EC of EAOC patients (p<0.01). Moreover, the high expression of RRM2 was consistent with the expression of Ki-67 in EC of EAOC patients.Conclusions: The upregulated expression of RRM2 in the EC of OE patients may indicate malignant transformation. RRM2 may be used as a marker of OE, which allows the investigation of the mechanism of the malignant transformation of OE.


2019 ◽  
Vol 9 (2) ◽  
pp. 12-19
Author(s):  
N. N. Bayramova ◽  
A. E. Protasova ◽  
G. A. Raskin ◽  
M. S. Sobivchak ◽  
M. I. Yarmolinskaya

Background. In 2016, the World Health Organization published an updated version of the Histological Classification for ovarian tumors presenting a new category of endometriosis-associated tumors. The predictors of malignant transformation of endometriosis have not been clearly defined so far.Purpose. The search for histological and immunohistochemical markers of endometriosis-associated malignancy.Materials and methods. 28 female patients with endometrioid ovarian cancer and 11 patients with clear cell ovarian carcinoma were enrolled. Histological and immunohistochemical studies were carried out using conventional techniques. Immunohistochemistry was applied to determine the hormone receptor status: expression of steroid hormone receptors, BAF250a (ARID1A), PTEN, P-catenin, MSH6, PMS2, р-53, WT-1, proliferative index (Ki-67). Microsatellite instability (MSI) testing was conducted according to the standard protocol.Results. In all cases of ovarian cancer, histological examination showed one of the endometriosis features. Atypical endometriosis was found in 39 % (11 / 28) of endometrioid tumors and in 9% (1/ 11) of clear cell carcinomas. Endometrioid ovarian cancer was found to be ER (74±7,8%) — and PR (67±5,4%) — positive; Ki-67 index was 68,2±3,7 %; loss of BAF250a (ARID1A) expression was observed in 14% (4/ 28), loss of PTEN expression in 29 % (8 / 28), nuclear expression of P-catenin in 32% (9/28) of cases. Loss of MMR expression was detected in 7% (2/28) of cases. MSI was found in one case only, which was also associated with loss of expression of BAF250a (ARID1A) and MSH6. Clear cell carcinoma of the ovary showed histological criteria for endometriosis; however, there were no changes immunohistochemical markers expression that were typical for endometriosis-associated malignancies. It could be due to a small number of patients in the group so further research is needed.Conclusion. Atypical endometriosis may be a morphological precursor of endometrioid and clear cell carcinoma of the ovary. Comprehensive assessment of a marker panel consisting of BAF250a (ARID1A), P-catenin, PTEN, p53, Ki-67 index, PMS2 and MSH6 will allow improving the diagnosis of atypical endometriosis and endometriosis-associated ovarian cancer.


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.


2016 ◽  
Vol 26 (5) ◽  
pp. 825-832 ◽  
Author(s):  
John P. Stamp ◽  
C. Blake Gilks ◽  
Martine Wesseling ◽  
Sima Eshragh ◽  
Kathy Ceballos ◽  
...  

Background and ObjectiveAtypical endometriosis (AE) is thought to be a precursor lesion to the ovarian cancer subtypes associated with endometriosis, namely, endometrioid and clear cell carcinomas.ARID1Aencodes a nuclear protein (BAF250a) governing chromatin remodeling, and mutations inARID1Ahave been found in 30% to 50% of clear cell and endometrioid ovarian cancers. As BAF250a expression loss by immunohistochemistry (IHC) has been documented in the endometriosis precursor lesions closely associated with these ovarian cancers subtypes, our goal was to further study the association between BAF250a expression in cases of AE with and without an associated cancer.MethodsThree separate databases were screened for suspected cases of AE. Based on a detailed review of the pathology reports, we selected cases likely to contain AE for slide review. After slide review, tissue blocks were recalled to perform IHC for BAF250a in the associated cancer, AE, or typical endometriosis when present.ResultsThere were 35 cases of endometriosis-associated cancer and 8 cases of AE not associated with cancer. Atypical endometriosis was found on pathology review in 23 endometriosis-associated cancer cases (66%). In the 35 cancer cases, BAF250a IHC showed loss of expression in 14 cases. Atypical endometriosis was present in 10 of these cases, 6 of which showed BAF250a loss (60%). BAF250a loss was not observed in the 8 cases of AE not associated with cancer or in the contiguous AE of 13 cases, whereby BAF250a expression was retained in the associated cancer.ConclusionsBAF250a loss in AE is consistently associated with the development of BAF250a-negative endometriosis-associated cancers and appears to be an early event in most of these cases. This research provides additional evidence that in the absence of cancer, BAF250a expression should be evaluated as a biomarker of cancer risk in patients diagnosed with AE.


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 146 (5) ◽  
pp. S-408
Author(s):  
Yezaz A. Ghouri ◽  
Sachin Batra ◽  
Nirav C. Thosani ◽  
Sushovan Guha

2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.


2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 179-182 ◽  
Author(s):  
M. Ueda ◽  
Y. Terai ◽  
K. Kanda ◽  
M. Kanemura ◽  
M. Takehara ◽  
...  

Single-nucleotide polymorphism at −670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas −670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08–6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05–2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter −670 may be associated with the risk of cervical cancer in a Japanese population.


2021 ◽  
Vol 11 (3) ◽  
pp. 178
Author(s):  
Noah R. Delapaz ◽  
William K. Hor ◽  
Michael Gilbert ◽  
Andrew D. La ◽  
Feiran Liang ◽  
...  

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.


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