scholarly journals Value of p53 and estrogen receptors immunohistochemical staining in endometrial carcinoma

Author(s):  
Dejan Opric ◽  
Amer Suskic ◽  
Sanela Halilovic Suskic ◽  
Gorana Nikolic ◽  
Isidora Filipovic

Background: Since there are many articles dealing with estimating prognostic and diagnostic value of ER and p53, using different, usually complex ICH interpretation methods, we wanted to evaluate significance of p53 and ER ICH positivity in endometrial carcinoma, using easily applicable criteria that would help pathologists and clinicians to be sure in ICH findings noted in the report.Methods: This paper deals with data of the patients treated for endometrial carcinoma in Public Hospitals in Travnik, gynecological department in the period from 1st January 2013 to 1st January 2019. The study included 97 women with endometrial carcinoma, with ages ranging from 42 to 90 years (mean of 64 years). Sample consisted of 72 cases (74.2%) of endometrioid and 25 cases (25.8%) of non-endometrioid carcinoma.Results: p53 expression was observed in 13.8% carcinomas of the endometrioid type and in 68% carcinomas of non-endometrioid type, while estrogen receptors were more frequently observed in tumors of the endometrioid type (61%) in contrast to non-endometrioid type (28%). Among 72 cases, those with grade I expressed estrogen receptors (26 out of 34 cases - 72%) more frequently than those with grades II and III. Frequency of p53 positivity was significantly higher at higher grades (grade I - 5.8%, grade II - 11.5%, grade III - 71.4%). Stage I carcinomas showed p53 staining less frequently (22.2%) that carcinomas diagnosed at later stages (31.5%).Conclusions: Using 80% nuclei stained as threshold for p53 positivity, we concluded that p53 is marker of high-grade endometrial carcinomas: high grade endometrioid and non-endometrioid carcinomas. Using 1% of cells as threshold for ER positivity, we confirmed that ER are common in endometrioid type carcinoma, in contrast to non-endometrioid type. Although observed, higher frequency of ER in tumors with lower grade and stage was not statistically confirmed in our study population.

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi246-vi246
Author(s):  
Jeffrey Olson ◽  
Brent Weinberg ◽  
Saumya Gurbani ◽  
Karthik Ramesh ◽  
Eduard Schreibmann ◽  
...  

Abstract Primary brain tumors are serious and life-threatening; thus, accurate histopathologic diagnosis is critical for determining the proper clinical treatment regimen. Grade II/III gliomas (lower grade gliomas, or LGGs), including astrocytomas and oligodendrogliomas, are heterogeneous and potentially contain low- and high-grade areas within the same tumor. Therefore, it is critical to target biopsies to the most aggressive portion of the tumor to avoid tumor under-grading and under-treatment. While glioblastomas are typically targeted based on contrast-enhanced MRI, LGGs have little contrast enhancement to define targets for biopsy treatment guidance. Spectroscopic MRI (sMRI) is a high-resolution MRI imaging method which allows for detection of metabolic abnormalities such as choline and NAA in the entire brain without injection of a contrast agent. We have previously evaluated the relationship between sMRI Cho/NAA ratios and tumor infiltration in surgical specimens from high grade gliomas, demonstrating a strong correlation between sMRI results and glioma infiltration. We also used the location information to correlate sMRI data to genetic and histologic biomarkers (such as 1p19q, IDH, and MGMT). An IRB-approved pilot study to obtain sMRI prior to stereotactic biopsy has been done in 20 non-enhancing LGG cases. Patients with a suspected LGG diagnosis underwent sMRI at the time of their surgical planning MRI. sMRI images were then registered to the T1w-CE and T2/FLAIR images and imported into the Stealth neuronavigation system for biopsy planning. We found that all astrocytomas (regardless of grades) showed strongly elevated Cho/NAA, while the LGGs were hardly delineated on T1w and T2/FLAIR. We found that pathology-confirmed grade II oligodendroglioma do not have choline elevation; however, NAA was mildly decreased, myo-inositol was elevated, and creatine (Cr) was mildly elevated. sMRI is a useful tool to improve biopsy targeting in LGG patients by ensuring that the highest risk regions are sampled.


2020 ◽  
Vol 102-B (12) ◽  
pp. 1752-1759
Author(s):  
Yusuke Tsuda ◽  
Kim Tsoi ◽  
Jonathan D. Stevenson ◽  
Minna Laitinen ◽  
Peter C. Ferguson ◽  
...  

Aims Our aim was to develop and validate nomograms that would predict the cumulative incidence of sarcoma-specific death (CISSD) and disease progression (CIDP) in patients with localized high-grade primary central and dedifferentiated chondrosarcoma. Methods The study population consisted of 391 patients from two international sarcoma centres (development cohort) who had undergone definitive surgery for a localized high-grade (histological grade II or III) conventional primary central chondrosarcoma or dedifferentiated chondrosarcoma. Disease progression captured the first event of either metastasis or local recurrence. An independent cohort of 221 patients from three additional hospitals was used for external validation. Two nomograms were internally and externally validated for discrimination (c-index) and calibration plot. Results In the development cohort, the CISSD at ten years was 32.9% (95% confidence interval (CI) 19.8% to 38.4%). Age at diagnosis, grade, and surgical margin were found to have significant effects on CISSD and CIDP in multivariate analyses. Maximum tumour diameter was also significantly associated with CISSD. In the development cohort, the c-indices for CISSD and CIDP at five years were 0.743 (95% CI 0.700 to 0.819) and 0.761 (95% CI 0.713 to 0.800), respectively. When applied to the validation cohort, the c-indices for CISSD and CIDP at five years were 0.839 (95% CI 0.763 to 0.916) and 0.749 (95% CI 0.672 to 0.825), respectively. The calibration plots for these two nomograms demonstrated good fit. Conclusion Our nomograms performed well on internal and external validation and can be used to predict CISSD and CIDP after resection of localized high-grade conventional primary central and dedifferentiated chondrosarcomas. They provide a new tool with which clinicians can assess and advise individual patients about their prognosis. Cite this article: Bone Joint J 2020;102-B(12):1752–1759.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5261
Author(s):  
Irati Hervás-Corpión ◽  
Andrea Gallardo-Orihuela ◽  
Inmaculada Catalina-Fernández ◽  
Irene Iglesias-Lozano ◽  
Olga Soto-Torres ◽  
...  

Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene Atlas and the REMBRANDT datasets plus a molecular examination of our own collection of surgical tumor resections. We determined a net reduction in the levels of the non-canonical histone H3 variant H3.3 in GB compared to lower-grade astrocytomas and oligodendrogliomas with a concomitant increase in the levels of the canonical histone H3 variants H3.1/H3.2. This increase can be potentially useful in the clinical diagnosis of high-grade gliomas, as evidenced by an immunohistochemistry screening of our cohort and can be at least partially explained by the induction of multiple histone genes encoding these canonical forms. Moreover, GBs showing low bulk levels of the H3.1/H3.2 proteins were more transcriptionally similar to low-grade gliomas than GBs showing high levels of H3.1/H3.2. In conclusion, this study identifies an imbalanced ratio between the H3 variants associated with glioma malignancy and molecular patterns relevant to the biology of gliomas, and proposes the examination of the H3.3 and H3.1/H3.2 levels to further refine diagnosis of low- and high-grade gliomas in future studies.


2004 ◽  
Vol 14 (2) ◽  
pp. 354-359 ◽  
Author(s):  
A. Abargel ◽  
I. Avinoach ◽  
V. Kravtsov ◽  
M. Boaz ◽  
M. Glezerman ◽  
...  

The aim of the study was to assess both p27 and p53 expression in the stromal and epithelial component of carcinosarcoma and to assess if their expression in the latter is different than in endometrial carcinoma. Immunohistochemical staining for p27 and p53 was performed on paraffin-embedded tissue blocks of 18 uterine specimens with carcinosarcoma and their expression assessed. Their expression in the epithelial element was also compared to that in 35 paraffin-embedded tissue blocks of endometrial endometrioid carcinoma.Reduced p27 expression was observed in a similarly high proportion of the stromal (77.8%) as well as of the epithelial component (66.7%) of carcinosarcoma. Although statistically not significant, the proportion of reduced p27 expression in endometrial carcinoma (85.7%) was higher than in the epithelial element of carcinosarcoma.The percentage of p53 overexpression in both elements of carcinosarcomas and in endometrial carcinomas was low and also similar (27.8 and 20.0%, respectively).Our results indicate that reduced p27 expression is common and p53 overexpression is infrequent in carcinosarcoma. Their similar rates of expression in the stromal and epithelial elements of the tumor support the contention of a monoclonal origin of carcinosarcoma. Unexpectedly, reduced p27 expression is more common in endometrial carcinoma than in the epithelial element of carcinosarcoma, in spite of the less favorable prognosticators and outcome in the latter.Further studies of p27 expression in carcinosarcoma are indicated to establish its clinical value in this aggressive malignancy.


Author(s):  
Dr. Suchandra Ray ◽  
Dr. Ashish Jha ◽  
Dr. Ayesha Afreen Islam ◽  
Dr. Moumita Sengupta

Background: Endometrial hyperplasia essentially implies an overgrowth of the endometrium. Complex hyperplasia associated with cellular atypia, seems to be the most important predictor of malignant potential. Endometrioid Endometrial Carcinomas account for three-fourths of Endometrial Carcinomas and are thought to develop following a continuum of premalignant lesions ranging from endometrial hyperplasia without atypia, to hyperplasia with atypia, and finally to well-differentiated carcinoma. Currently the most frequently observed gene mutation in endometrioid carcinoma is located on chromosome 10 and is related with the PTEN gene (phoshatase and tensin homolog). PTEN inactivation is found to correlate with clonal growth pattern detected in endometrial hyperplasia and carcinoma. The p53 tumor suppressor gene locates to chromosome 17p13. The abnormal p53 expression has been found in 11% of grade 1 endometrioid endometrial carcinoma, while p53 mutations occur in 90% of non-endometrioid endometrial carcinoma. Aims and objectives: In this study we aim to evaluate the immuno histochemical expression of P53 and PTEN genes in endometrial hyperplasia and endometrial carcinoma and correlate their expression with prognostic outcomes like grade and stage, in cases of endometrial carcinoma. Material and methods: A prospective study of 60 patients with abnormal uterine bleed in the peri and post menopausal age was conducted, for a period of three years. Histological specimens were studied for HPE and IHC for the markers PTEN and P53. Results: The mean age for hyperplastic and carcinomatous lesions was 44.9 years and 53.2 years respectively. 35% (21 cases) were endometrial hyperplasia and 65% (39 cases) of cases were endometrial carcinoma. Among endometrial carcinoma 87% are of endometrioid type and 13% are of other types, which include serous, clear and malignant mixed Mullerian type of carcinoma. IHC study showed that PTEN expression is higher in endometrial hyperplasia than endometrial carcinoma cases. Elevated P53 expression correlated with poor differentiation of endometrial cancer. P53 was found to be more in cases with FIGO staging III &IV compared to stage I & II (100% vs 18.1% p value= 0.0016) and grade 3 compared to grade 1&2 (50% vs 0 p value= 0.0116).   Conclusion: Immuno histochemical biomarkers like PTEN and P53 may contribute to better tumor characterization and thus more precisely determine its clinical behavior.  Key words: endometrial hyperplasia, endometrial carcinoma, PTEN, P53.


2013 ◽  
Vol 27 (2) ◽  
pp. 255-261 ◽  
Author(s):  
Ghassan Allo ◽  
Marcus Q Bernardini ◽  
Ren-Chin Wu ◽  
Ie-Ming Shih ◽  
Steve Kalloger ◽  
...  

2001 ◽  
Vol 11 (4) ◽  
pp. 272-276 ◽  
Author(s):  
N. Nishimura ◽  
T. Hachisuga ◽  
T. Saito ◽  
T. Kawarabayashi

Abstract.Nishimura N, Hachisuga T, Saito T, Kawarabayashi T. Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients.This study aimed to detail the clinicopathologic features of endometrial carcinomas that developed in Japanese patients receiving adjuvant tamoxifen treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen-treated breast cancer patients were collected from two medical centers. The endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The tumor was limited to the endometrium in two cases. Myometrial invasion was limited to the inner half of the myometrium in five cases and involved the outer half in three. A mild degree of lymphovascular space invasion was identified in five cases. Deep cervical invasion was recognized in one case. The cell types comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of eight postmenopausal endometrial carcinomas were associated with polypoid endometrial lesions composed of cystically dilated atrophic and proliferative glands widely separated by fibrotic stroma. Two patients with retroperitoneal lymph node metastases died of endometrial cancer. One patient developed a contralateral breast cancer during tamoxifen treatment. No patient died of breast cancer. We did not demonstrate a higher frequency of either high-grade tumors or unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer patients.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii159-ii160
Author(s):  
Roberta Rudà ◽  
Riccardo Pascuzzo ◽  
Francesca Mo ◽  
Alessia Pellerino ◽  
Peter B Barker ◽  
...  

Abstract BACKGROUND There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy. MATERIAL AND METHODS We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii426-iii426
Author(s):  
Dominik Sturm ◽  
Felix Sahm ◽  
Felipe Andreiuolo ◽  
David Capper ◽  
Marco Gessi ◽  
...  

Abstract The large variety of CNS tumor entities affecting children and adolescents, some of which are exceedingly rare, results in very diverging patient outcomes and renders accurate diagnosis challenging. To assess the diagnostic utility of routine DNA methylation-based CNS tumor classification and gene panel sequencing, the Molecular Neuropathology 2.0 study prospectively integrated these (epi-)genetic analyses with reference neuropathological diagnostics as an international trial for newly-diagnosed pediatric patients. In a four-year period, 1,215 patients with sufficient tissue were enrolled from 65 centers, receiving a reference neuropathological diagnosis according to the WHO classification in >97%. Using 10 FFPE sections as input, DNA methylation analysis was successfully performed in 95% of cases, of which 78% with sufficient tumor cell content were assigned to a distinct epigenetic tumor class. The remaining 22% did not match any of 82 represented classes, indicating novel rare tumor entities. Targeted gene panel sequencing of >130 genes performed for 96% of patients with matched blood samples detected diagnostically, prognostically, or therapeutically relevant somatic alterations in 48%. Germline DNA sequencing data indicated potential predisposition syndromes in ~10% of patients. Discrepant results by neuropathological and epigenetic classification (29%) were enriched in histological high-grade gliomas and implicated clinical relevance in 5% of all cases. Clinical follow-up suggests improved survival for some patients with high-grade glioma histology and lower-grade molecular profiles. Routine (epi-)genetic profiling at the time of primary diagnosis adds a valuable layer of information to neuropathological diagnostics and will improve clinical management of CNS tumors.


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