Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica

Detalhes bibliográficos
Autor(a) principal: Feitosa, Priscilla Mariana Freitas Aguiar
Data de Publicação: 2023
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://repositorio.ufc.br/handle/riufc/74901
Resumo: Prostate cancer is the most diagnosed male malignancy in worldwide. Recent work suggests that the rate of microsatellite instability (MSI) in primary prostate tumors is <4% and suggests that patients with higher ERG expression intensity were significantly more likely to develop biochemical relapse, metastasis, and prostate cancer-specific mortality. The objective was tocorrelate gene expression of PMS2, MSH6 and ERG with classic pathological clinical prognostic markers. For this, a retrospective cohort was constituted, and tissue microarray immunohistochemistry (TMA) reactions were performed on samples taken from non-neoplastic and neoplastic tissues, characterizing, evaluating, relating, and comparing the expression of PMS2, MSH6 and ERG markers. It was a total of 680 samples from adenocarcinoma patients undergoing radical prostatectomy, after following exclusion criteria a 635 samples remained. Age over 60 years showed odds ratios in relation to the absence of PMS2 and MSH6 marking equal to 4.31 and 1.58, respectively. There was no significant difference in relation to marked MSH6, PMS2 and ERG and PSA levels above 10 ng/ml. Individuals who did not have positive MSH6 labeling have an odds ratio of 6.40 for biochemical recurrence. There is no statistically significant difference between the groups that marked and did not mark MSH2 with respect to biochemical recurrence. The group who did not mark MSH6 and/or PMS2 had higher Gleason scores and there is no statistically significant difference between the Gleason score values (pooled) between individuals who marked and those who did not mark ERG. The group of patients who did not score MSH6 showed worse pictures regarding staging.There is a higher frequency of metastasis among patients without MSH6 marking. There is no statistically significant difference regarding the presence of ERG or absence of PMS2 and presence of metastasis. MSH6 and PMS2 markers were not significantly associated with many of the evolutionary outcomes evaluated, a fact that we can explain due to the fact that our patients belonged to the low-risk group. Of the ERG positive patients (190/635), two with weak and focal marking, seven with moderate marking and two with marked marking showed metastasis. In conclusion, age over 60 years was not statistically significant in relation to the presence of ERG and absence of PMS2 and MSH6 marking. Negative MSH6 labeling and/or positive ERG labeling shows a relationship with biochemical recurrence. Gene expression of PMS2, MSH6 and ERG had no association with PSA levels above 10 ng/ml. Gleason score values were higher in the group that did not tag MSH6 and/or PMS2 and there was no association with the presence or absence of ERG tagging. There is evidence that there is a difference in staging between the groups that did and did not mark PMS2 and ERG and that there is a higher frequency of metastasis among patients without MSH6 marking. In addition, patients with moderate to strong ERG labeling have higher staging compared to the others. Further studies should be conducted to corroborate the elements cited and future work can use these data for associations with other clinical outcomes.
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spelling Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológicaNeoplasias da PróstataProstatectomiaImuno-HistoquimicaPrognósticoProstate cancer is the most diagnosed male malignancy in worldwide. Recent work suggests that the rate of microsatellite instability (MSI) in primary prostate tumors is <4% and suggests that patients with higher ERG expression intensity were significantly more likely to develop biochemical relapse, metastasis, and prostate cancer-specific mortality. The objective was tocorrelate gene expression of PMS2, MSH6 and ERG with classic pathological clinical prognostic markers. For this, a retrospective cohort was constituted, and tissue microarray immunohistochemistry (TMA) reactions were performed on samples taken from non-neoplastic and neoplastic tissues, characterizing, evaluating, relating, and comparing the expression of PMS2, MSH6 and ERG markers. It was a total of 680 samples from adenocarcinoma patients undergoing radical prostatectomy, after following exclusion criteria a 635 samples remained. Age over 60 years showed odds ratios in relation to the absence of PMS2 and MSH6 marking equal to 4.31 and 1.58, respectively. There was no significant difference in relation to marked MSH6, PMS2 and ERG and PSA levels above 10 ng/ml. Individuals who did not have positive MSH6 labeling have an odds ratio of 6.40 for biochemical recurrence. There is no statistically significant difference between the groups that marked and did not mark MSH2 with respect to biochemical recurrence. The group who did not mark MSH6 and/or PMS2 had higher Gleason scores and there is no statistically significant difference between the Gleason score values (pooled) between individuals who marked and those who did not mark ERG. The group of patients who did not score MSH6 showed worse pictures regarding staging.There is a higher frequency of metastasis among patients without MSH6 marking. There is no statistically significant difference regarding the presence of ERG or absence of PMS2 and presence of metastasis. MSH6 and PMS2 markers were not significantly associated with many of the evolutionary outcomes evaluated, a fact that we can explain due to the fact that our patients belonged to the low-risk group. Of the ERG positive patients (190/635), two with weak and focal marking, seven with moderate marking and two with marked marking showed metastasis. In conclusion, age over 60 years was not statistically significant in relation to the presence of ERG and absence of PMS2 and MSH6 marking. Negative MSH6 labeling and/or positive ERG labeling shows a relationship with biochemical recurrence. Gene expression of PMS2, MSH6 and ERG had no association with PSA levels above 10 ng/ml. Gleason score values were higher in the group that did not tag MSH6 and/or PMS2 and there was no association with the presence or absence of ERG tagging. There is evidence that there is a difference in staging between the groups that did and did not mark PMS2 and ERG and that there is a higher frequency of metastasis among patients without MSH6 marking. In addition, patients with moderate to strong ERG labeling have higher staging compared to the others. Further studies should be conducted to corroborate the elements cited and future work can use these data for associations with other clinical outcomes.Em todo o mundo, o câncer de próstata é a doença maligna masculina mais comumente diagnosticada. Trabalhos recentes sugerem que a taxa de instabilidade de microssatélites (MSI) em tumores de próstata primários é <4%, além de sugerir que pacientes com maior intensidade de expressão ERG foram significativamente mais propensos a desenvolver recaída bioquímica, metástases e mortalidade específica para câncer de próstata. Objetivou-se correlacionar a expressão gênica de PMS2, MSH6 e ERG com marcadores prognósticos clínicos patológicos clássicos. Para tanto, constituiu-se coorte retrospectiva e realizaram-se reações de imuno-histoquímica (IHQ) em tissue microarray (TMA) de amostras retiradas de tecido não neoplásico e neoplásico, caracterizando, avaliando, relacionando e comparando as expressões dos marcadores PMS2, MSH6 e ERG. Foi um total de 680 amostras de pacientes com adenocarcinoma submetidos a prostatectomia radical, após seguir os critérios de exclusão restou 635 amostras; e foi utilizado o valor-p abaixo de 0,05 para estatisticamente significante.Não há diferença estatisticamente significativa entre os grupos que marcaram e não marcaram PMS2 em relação a recorrência bioquímica, além de quanto a ausência de PMS2 e a presença de metástase.Indivíduos com marcação negativa de MSH6 apresentam razão de chances de 6.40 para a recorrência bioquímica.Há maior frequência de metástase entre os pacientes sem marcação MSH6. O grupo de pacientes que não marcaram MSH6 apresentou piores quadros referentes ao estadiamento.A idade superior a 60 anos apresentou razões de chances em relação à ausência de marcação PMS2 e MSH6 iguais a, respectivamente, 4.31 e 1.58. O grupo que não marcou PMS2 e/ou MSH6 teve maiores escores de Gleason. Os marcadores PMS2 e MSH6 não se associaram de forma significativa com muitos dos desfechos evolutivos avaliados, fato que podemos explicar devido ao fato dos nossos pacientes pertencerem a grupo de baixo risco.Não há diferença estatisticamente significante entre os valores de escores de Gleason (agrupados) entre os indivíduos que marcaram e os que não marcaram ERG, além de quanto a presença de ERG e presença de metástase.Dos pacientes com ERG positivo (190/635), dois com marcação fraca e focal, setecom marcação moderadae doiscom marcação acentuada apresentaram metástase.Não houve diferença significativa em relação aos marcados MSH6, PMS2 e ERG e níveis de PSA acima de 10 ng/ml.Em conclusão, não há diferença no estadiamento patológico entre os grupos que marcaram e não PMS2. Há maior frequência de metástase entre os pacientes sem marcação MSH6. Marcação negativa de MSH6 apresenta relação com recorrência bioquímica. Pacientes que não marcaram MSH6 apresentaram piores estadiamentos. A idade superior a 60 anos não está relacionada com a ausência de marcação do PMS2 e do MSH6. Os valores de Gleason foram maiores no grupo que não marcou PMS2 e/ou MSH6. Marcação positiva de ERG apresenta relação com recorrência bioquímica. Pacientes com marcação moderada a forte de ERG tem estadiamento mais elevado quando comparado com os demais.Pacientes com marcação moderada a forte de ERG tem estadiamento mais elevado.Não houve associação com a presença ou ausência da marcação ERG e os valores de Gleason. Idade superior a 60 anos não está relacionada com a presença de marcação ERG. Nenhum aumento de metástase foi detectado em pacientes com expressão ERG mais intensa.A expressão gênica de PMS2, MSH6 e ERG não teve associação com níveis de PSA acima de 10 ng/ml.Mais estudos devem ser realizados para corroborar com os elementos citados e trabalhos futuros podem usar esses dados para associações com outros desfechos clínicos.Dornelas, Conceição AparecidaFeitosa, Priscilla Mariana Freitas Aguiar2023-11-07T14:18:31Z2023-11-07T14:18:31Z2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfFEITOSA, Priscilla Mariana Freitas Aguiar. Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica. 2023. Dissertação (Mestrado em Patologia) – Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74901. Acesso em: 07 nov. 2023.http://repositorio.ufc.br/handle/riufc/74901info:eu-repo/semantics/embargoedAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFC2023-11-07T14:22:29Zoai:repositorio.ufc.br:riufc/74901Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:49:30.296070Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
title Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
spellingShingle Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
Feitosa, Priscilla Mariana Freitas Aguiar
Neoplasias da Próstata
Prostatectomia
Imuno-Histoquimica
Prognóstico
title_short Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
title_full Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
title_fullStr Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
title_full_unstemmed Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
title_sort Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica
author Feitosa, Priscilla Mariana Freitas Aguiar
author_facet Feitosa, Priscilla Mariana Freitas Aguiar
author_role author
dc.contributor.none.fl_str_mv Dornelas, Conceição Aparecida
dc.contributor.author.fl_str_mv Feitosa, Priscilla Mariana Freitas Aguiar
dc.subject.por.fl_str_mv Neoplasias da Próstata
Prostatectomia
Imuno-Histoquimica
Prognóstico
topic Neoplasias da Próstata
Prostatectomia
Imuno-Histoquimica
Prognóstico
description Prostate cancer is the most diagnosed male malignancy in worldwide. Recent work suggests that the rate of microsatellite instability (MSI) in primary prostate tumors is <4% and suggests that patients with higher ERG expression intensity were significantly more likely to develop biochemical relapse, metastasis, and prostate cancer-specific mortality. The objective was tocorrelate gene expression of PMS2, MSH6 and ERG with classic pathological clinical prognostic markers. For this, a retrospective cohort was constituted, and tissue microarray immunohistochemistry (TMA) reactions were performed on samples taken from non-neoplastic and neoplastic tissues, characterizing, evaluating, relating, and comparing the expression of PMS2, MSH6 and ERG markers. It was a total of 680 samples from adenocarcinoma patients undergoing radical prostatectomy, after following exclusion criteria a 635 samples remained. Age over 60 years showed odds ratios in relation to the absence of PMS2 and MSH6 marking equal to 4.31 and 1.58, respectively. There was no significant difference in relation to marked MSH6, PMS2 and ERG and PSA levels above 10 ng/ml. Individuals who did not have positive MSH6 labeling have an odds ratio of 6.40 for biochemical recurrence. There is no statistically significant difference between the groups that marked and did not mark MSH2 with respect to biochemical recurrence. The group who did not mark MSH6 and/or PMS2 had higher Gleason scores and there is no statistically significant difference between the Gleason score values (pooled) between individuals who marked and those who did not mark ERG. The group of patients who did not score MSH6 showed worse pictures regarding staging.There is a higher frequency of metastasis among patients without MSH6 marking. There is no statistically significant difference regarding the presence of ERG or absence of PMS2 and presence of metastasis. MSH6 and PMS2 markers were not significantly associated with many of the evolutionary outcomes evaluated, a fact that we can explain due to the fact that our patients belonged to the low-risk group. Of the ERG positive patients (190/635), two with weak and focal marking, seven with moderate marking and two with marked marking showed metastasis. In conclusion, age over 60 years was not statistically significant in relation to the presence of ERG and absence of PMS2 and MSH6 marking. Negative MSH6 labeling and/or positive ERG labeling shows a relationship with biochemical recurrence. Gene expression of PMS2, MSH6 and ERG had no association with PSA levels above 10 ng/ml. Gleason score values were higher in the group that did not tag MSH6 and/or PMS2 and there was no association with the presence or absence of ERG tagging. There is evidence that there is a difference in staging between the groups that did and did not mark PMS2 and ERG and that there is a higher frequency of metastasis among patients without MSH6 marking. In addition, patients with moderate to strong ERG labeling have higher staging compared to the others. Further studies should be conducted to corroborate the elements cited and future work can use these data for associations with other clinical outcomes.
publishDate 2023
dc.date.none.fl_str_mv 2023-11-07T14:18:31Z
2023-11-07T14:18:31Z
2023
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dc.identifier.uri.fl_str_mv FEITOSA, Priscilla Mariana Freitas Aguiar. Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica. 2023. Dissertação (Mestrado em Patologia) – Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74901. Acesso em: 07 nov. 2023.
http://repositorio.ufc.br/handle/riufc/74901
identifier_str_mv FEITOSA, Priscilla Mariana Freitas Aguiar. Proteínas de reparo (PMS2 E MSH6) e ERG e seu papel no câncer de próstata em prostatectomias radicais: correlação clínico patológica. 2023. Dissertação (Mestrado em Patologia) – Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74901. Acesso em: 07 nov. 2023.
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