10P Clinical and morphological pattern of malignant tumors with microsatellite instability (MSI)

Histopathological evaluation of ovarian tumours in southern part of Assam

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20211356 ◽

2021 ◽

Vol 9 (4) ◽

pp. 1090

Author(s):

Madhusmita Choudhury ◽

Monoj K. Deka ◽

Shah A. Sheikh

Keyword(s):

Germ Cell ◽

Malignant Tumors ◽

Age Groups ◽

Germ Cell Tumors ◽

Reproductive Age ◽

Histopathological Study ◽

Age Group ◽

Malignant Tumours ◽

Morphological Pattern ◽

Ovarian Tumours

Background: Ovarian malignancy is the second most common cancer of the female reproductive system and the leading cause of death from gynecologic malignancy. With increase in longevity, the incidence of epithelial ovarian cancer is increasing and its etiopathology remains unknown. A female’s risk at birth of having ovarian tumour sometime in her life is 6-7%. Two third of ovarian tumours occur in women of reproductive age group. The aim was to study the distribution of morphological pattern of benign, malignant, and nonneoplastic lesions of the ovary in different age groups and to determine the likelihood of bilateral involvement in different morphologic subtypes.Methods: A retrospective study from January 2018 to December 2020 was undertaken. A total of 210 surgical specimens were obtained. Detailed clinical information and radiological findings were recorded from the case sheets. Grossing of the surgical specimens was done in the pathology department, followed by histological examination.Results: Of 210 cases, benign cases were 140 (66.7%), malignant cases were 70 (33.3%). Surface epithelial tumors were most common (116/55.2%) followed by germ cell tumors (76, 36.1%) followed by others. Serous cystadenoma was commonest benign tumor (58, 41.4%). Serous adenocarinoma was commonest malignant tumor (19, 27.1%). Benign tumours were more common in the younger age group i.e. <40 years of age whereas malignant tumours were supervenes with increase in age. Most benign ovarian tumors (54, 38.6%) were seen between 31-40 years whereas most malignant tumors (24, 34.3%) were seen above 40 years. In 1st two decades, germ cell tumors were more common than other tumours.Conclusions: The prognosis and varying therapeutic strategies of ovarian tumours necessitate an accurate pathological evaluation. Histopathological study is still the gold standard in diagnosing most of these tumours.

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Study of microsatellite instability in neuroendocrine tumors of pancreas and colon.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16196 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16196-e16196

Author(s):

Vladimir S. Trifanov ◽

Natalya N. Timoshkina ◽

Dmitry Yu. Gvaldin ◽

Milana Yu. Mesheryakova ◽

Evgeniy N. Kolesnikov ◽

...

Keyword(s):

Small Intestine ◽

Microsatellite Instability ◽

Malignant Tumors ◽

Distant Metastases ◽

Fragment Analysis ◽

Pancreatic Net ◽

Small Intestinal ◽

High Level ◽

High Immunogenicity ◽

Mlh1 Methylation

e16196 Background: Microsatellite instability (MSI), as an acquired feature of malignant tumors, is a predictive and prognostic marker. The less aggressive nature of MSI-positive tumors has been associated with high immunogenicity. In the present study, MSI was assessed in NET samples of different localizations. Methods: The sample included 50 patients with a diagnosis of pancreatic NET (G1-G3) and NET of colon (G2-G3). MSI was analyzed by fragment analysis of five microsatellite loci (Bat25, Bat26, NR21, NR24, NR27). The level of MLH1 methylation was detected by pyrosequencing. Results: MSI was noted in 25.8% cases of the NET of colon and in 13.3% cases of the NET of the pancreas. In the case of pancreatic NET, only MSI low level was identified (instability at 1/5 loci), while in the case of NET of colon, most cases were classified as MSI high level. The incidence of MSI of pancreatic NET was consistent with literature data for small intestinal NET (14%), unlike MSI NET and BRAF V600 mutated adenocarcinomas of colon, MSI-positive pancreatic NET were not associated with hypermethylation of the MLH1 promoter. MSI was more often detected in women over 60 years old, at stages of the tumor process without distant metastases (p = 0.49). The sample size did not allow us to determine significant differences in the studied clinical and pathological groups of NETs, however, we note that in all cases of an unfavorable course of the disease (progression, death), was noted MSS status of tumors. Conclusions: Thus, MSI-positive NET of colon resembles MSI-positive adenocarcinomas of colon in frequency and pathogenetic mechanisms, while in terms of the identified frequency of MSI in pancreatic NET resembles the NET of the small intestine.

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Bracken fern-induced malignant tumors in rats: absence of mutations in p53, H-ras and K-ras and no microsatellite instability

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/s0027-5107(01)00275-5 ◽

2002 ◽

Vol 499 (2) ◽

pp. 189-196 ◽

Cited By ~ 12

Author(s):

Renata N. Freitas ◽

Geraldo Brasileiro-Filho ◽

Marcelo E. Silva ◽

Sérgio D.J. Pena

Keyword(s):

Microsatellite Instability ◽

Malignant Tumors ◽

Bracken Fern

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Mutation analysis of multiple pilomatricomas in a patient with myotonic dystrophy type 1 suggests a DM1-associated hypermutation phenotype

10.1101/844647 ◽

2019 ◽

Author(s):

Albert Rübben ◽

Renate Ursula Wahl ◽

Thomas Eggermann ◽

Edgar Dahl ◽

Nadina Ortiz-Brüchle ◽

...

Keyword(s):

Microsatellite Instability ◽

Mismatch Repair ◽

Myotonic Dystrophy ◽

Malignant Tumors ◽

Point Mutations ◽

Hair Follicles ◽

Myotonic Dystrophy Type 1 ◽

Myotonic Dystrophy Type ◽

Mismatch Repair Proteins

AbstractMyotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease which results from an expansion of repetitive DNA elements within the 3’ untranslated region of the DMPK gene. Some patients develop multiple pilomatricomas as well as malignant tumors in other tissues. Mutations of the catenin-β gene (CTNNB1) could be demonstrated in most non-syndromic pilomatricomas.In order to gain insight into the molecular mechanisms which might be responsible for the occurrence of multiple pilomatricomas and cancers in patients with DM1, we have sequenced the CTNNB1 gene of four pilomatricomas and of one pilomatrical carcinoma which developed in one patient with molecularly proven DM1 within 4 years. We further analyzed the pilomatrical tumors for microsatellite instability as well as by NGS for mutations in 161 cancer-associated genes.Somatic and independent point-mutations were detected at typical hotspot regions of CTNNB1 (S33C, S33F, G34V, T41I) while one mutation within CTNNB1 represented a duplication mutation (G34dup.). Pilomatricoma samples were analyzed for microsatellite instability and expression of mismatch repair proteins but no mutated microsatellites could be detected and expression of mismatch repair proteins MLH1, MSH2, MSH6, PMS2 was not perturbed. NGS analysis only revealed one heterozygous germline mutation c.8494C>T; p.(Arg2832Cys) within the ataxia telangiectasia mutated gene (ATM) which remained heterozygous in the pilomatrical tumors.The detection of different somatic mutations in different pilomatricomas and in the pilomatrical carcinoma as well as the observation that the patient developed multiple pilomatricomas and one pilomatrical carcinoma over a short time period strongly suggest that the patient displays a hypermutation phenotype. This hypermutability seems to be tissue and gene restricted. Co-translation of the mutated DMPK gene and the CTNNB1 gene in cycling hair follicles might constitute an explanation for the observed tissue and gene specificity of hypermutability observed in DM1 patients. Elucidation of putative mechanisms responsible for hypermutability in DM1 patients requires further research.Author summaryLess than 10% of patients with myotonic dystrophy type 1 (DM1), an inherited and the most common neuromuscular disorder, develop pilomatricomas, often as multiple tumors. Pilomatricomas are benign skin tumors deriving from hair matrix cells, and they are very rare in the general population. Recently it could be demonstrated that DM1 patients also harbour and enhanced risk for benign and malignant tumors in various other tissues.DM1 is characterized genetically by an expansion of trinucleotide repeats within the 3’ untranslated region of the DMPK gene (DM1 protein kinase). It could be demonstrated that these expanded CTG-repeats are transcribed into RNA and that this non-translated repetitive RNA forms aggregates with various splicing regulators, which in turn impair transcription of multiple genes in various tissues. Following the gain-of-function-RNA hypothesis, Mueller and colleagues suggested in 2009 that the untranslated repetitive RNA directly enhances expression of β-catenin resulting in pilomatricomas as well as in various cancers which rely on activation of the WNT/APC/β-catenin pathway.In order to prove or to reject this hypothesis we have sequenced the CTNNB1 gene of four pilomatricomas and of one pilomatrical carcinoma which developed in one patient with molecularly proven DM1 within 4 years. Somatic and independent point-mutations were detected at typical hotspot regions of CTNNB1 (S33C, S33F, G34V, T41I) while one mutation within CTNNB1 represented a duplication mutation (G34dup.). We further analyzed the pilomatrical tumors for microsatellite instability but no mutated microsatellites could be detected and expression of mismatch repair proteins MLH1, MSH2, MSH6, PMS2 was not perturbed. NGS analysis in 161 cancer-associated genes only revealed one heterozygous germline mutation c.8494C>T; p.(Arg2832Cys) within the ataxia telangiectasia mutated gene (ATM) which remained heterozygous in the pilomatrical tumors.The detection of different somatic mutations in different pilomatricomas and in the pilomatrical carcinoma does not support the hypothesis that untranslated repetitive RNA directly enhances expression of β-catenin resulting in pilomatricomas. In contrast, our results strongly suggest that the patient displays a tissue and gene restricted hypermutation phenotype. One putative mechanism for the assumed gene and tissue restriction could be co-translation of the mutated DMPK gene and the CTNNB1 gene in cycling hair follicles.

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Immune checkpoint inhibitors in malignancies with mismatch repair deficiency: a review of the state of the current knowledge

Journal of Investigative Medicine ◽

10.1136/jim-2016-000342 ◽

2017 ◽

Vol 65 (4) ◽

pp. 754-758 ◽

Cited By ~ 22

Author(s):

Ali Naboush ◽

Christopher A J Roman ◽

Iuliana Shapira

Keyword(s):

Microsatellite Instability ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Malignant Tumors ◽

Current Knowledge ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Stage Iv ◽

Progression Free Survival ◽

Manual Search

The use of immune checkpoint inhibitors to treat malignant tumors with microsatellite instability is an emerging new modality. This is based on the observations that these tumors may have a high mutation rate—thus a potential source of tumor-specific neoantigens—and harbor infiltrating cytotoxic T cells in response, suggesting that they may be particularly susceptible to immune checkpoint therapy. PUBMED and ASCO library were systematically reviewed to identify all relevant data that involved the use of immune checkpoint inhibitors in the treatment of cancers with microsatellite instability. The manual search retrieved a total of 3 relevant articles and 1 abstract published between 2015 and 2016. A total of 61 patients with colorectal, 3 with ampullary/cholangiocarcinoma, 2 with endometrial carcinomas, 3 with small bowel cancers, 2 with glioblastoma multiforme, and 1 with bladder cancer with reported efficacy results were reviewed. All the patients had stage IV cancer and were treated with immune checkpoint inhibitors until progression of disease or intolerable side effects emerged. The range of objective response rate was 25–71%. Responses were also durable with progression-free survival at 20 weeks of around 67–78% and to 46% at 1 year. The use of immune checkpoint inhibitors is effective in cancers that express microsatellite instability.

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The application of electron microscopy to diagnosis in gynecologic neoplasms and tumor-like conditions

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100110787 ◽

1984 ◽

Vol 42 ◽

pp. 102-105

Author(s):

Lawrence M. Roth

Keyword(s):

Electron Microscopy ◽

Reproductive Tract ◽

Malignant Tumors ◽

Frozen Section ◽

Cost Effective ◽

Female Reproductive Tract ◽

Ultrastructural Examination ◽

Specific Diagnosis ◽

Potential Value ◽

Gynecologic Neoplasms

The female reproductive tract may be the site of a wide variety of benign and malignant tumors, as well as non-neoplastic tumor-like conditions, most of which can be diagnosed by light microscopic examination including special stains and more recently immunoperoxidase techniques. Nevertheless there are situations where ultrastructural examination can contribute substantially to an accurate and specific diagnosis. It is my opinion that electron microscopy can be of greatest benefit and is most cost effective when applied in conjunction with other methodologies. Thus, I have developed an approach which has proved useful for me and may have benefit for others. In cases where it is deemed of potential value, glutaraldehyde-fixed material is obtained at the time of frozen section or otherwise at operation. Coordination with the gynecologic oncologist is required in the latter situation. This material is processed and blocked and is available if a future need arises.

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Ultrastructure of Cryptorchidism and Seminoma

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099143 ◽

1981 ◽

Vol 39 ◽

pp. 540-541

Author(s):

Shirley Siew ◽

Susan C. James

Keyword(s):

Malignant Tumors ◽

Frozen Section ◽

Malignant Potential ◽

Genetic Influences ◽

Endocrine Gland ◽

Medial Aspect ◽

Left Testis ◽

Bilateral Orchiectomy

Testicular maldescent is the most common endocrine gland abnormality, as 2.7% of mature neonates are cryptorchid. The significant complications are that there is a disturbance of normal maturation which results in diminished fertility and there is an increase in the malignant potential which is 35 times greater in the undescended than the descended testis. It is considered that genetic influences may be of etiological importance and recurrence has been described in some families. It is of interest, that the case reported here has 2 siblings who have also presented with cryptorchidism and malignant tumors.The propositus is 14 years old. He is well developed (described by some as obese) and shows normal secondary male characteristics except for an immature scrotum. Laparotomy showed both testes to be intraabdominal. A hard nodule (0.5cm) was palpated on the medial aspect of the left testis. Frozen section showed the presence of seminoma and bilateral orchiectomy was performed.

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Hepatocyte ultrastructural alterations in perimetastatic areas

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166300 ◽

1996 ◽

Vol 54 ◽

pp. 768-769

Author(s):

H. J. Finol ◽

M. E. Correa ◽

L.A. Sosa ◽

A. Márquez ◽

N.L. Díaz

Keyword(s):

Malignant Tumor ◽

Malignant Tumors ◽

Surrounding Tissue ◽

Ultrastructural Changes ◽

Pancreas Carcinoma ◽

Duct Carcinoma ◽

Tissue Samples ◽

Primary Malignant Tumor ◽

Transmission Electron ◽

Remote Sites

In classical oncological literature two mechanisms for tissue aggression in patients with cancer have been described. The first is the progressive invasion, infiltration and destruction of tissues surrounding primary malignant tumor or their metastases; the other includes alterations produced in remote sites that are not directly affected by any focus of disease, the so called paraneoplastic phenomenon. The non-invaded tissue which surrounds a primary malignant tumor or its metastases has been usually considered a normal tissue . In this work we describe the ultrastructural changes observed in hepatocytes located next to metastases from diverse malignant tumors.Hepatic biopsies were obtained surgically in patients with different malignant tumors which metatastized in liver. Biopsies included tumor mass, the zone of macroscopic contact between the tumor and the surrounding tissue, and the tissue adjacent to the tumor but outside the macroscopic area of infiltration. The patients (n = 5), 36–75 years old, presented different tumors including rhabdomyosarcoma, leiomyosarcoma, pancreas carcinoma, biliar duct carcinoma and colon carcinoma. Tissue samples were processed with routine techniques for transmission electron microscopy and observed in a Hitachi H-500 electron microscope.

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