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Previous issue date: 2013-10-16 / Endocervical and Endometrial Adenocarcinomas are uterine neoplasms with different biological behaviors and different treatments, being all the therapeutic plan based on the origin site of these tumors. To differentiate these two neoplasms, many times the immunohistochemical study is used as an ancillary tool to assist and complement histopathological examination. Previous studies have investigated the value of various markers in the distinction of these neoplasms, with results varying and sometimes conflicting. In this study the impact of the MCM2, bcl2 and villin markers in the differential diagnosis of endocervical and endometrial adenocarcinomas, associated or not to a traditional markers panel formed by CEA, vimentin, RE, RP and p16, was evaluated. Material and methods: A tissue microarray (TMA) was constructed using paraffin-embedded, formalin-fixed tissues from 104 hysterectomy specimens and conizations. Out of the 104, 51 samples were represented by unequivocal cases of adenocarcinomas of the endocervice and 53 represented unequivocal cases of endometrial adenocarcinomas. The sections of tissue microarray block were immunostained with the eight antibodies in study and to the antigen-antibody reaction preview it was used the polymer detection system. Scoring of immunostaining was interpreted using the German semi quantitative scoring system in considering the staining intensity and area extent of marker expression. The final Immunoreactive score was determined by multiplying the positive intensity and the positive area extent scores. The threshold for differentiating between final positive and negative immunostaining was set at 4 for interpretation (0-3 = negative; 4-12 = positive). Results: The univariate analysis showed that out of the eight markers, seven (CEA, vimentin, RE, RP, p16, MCM2 and bcl2) showed good performance in the distinction between the endocervical and endometrial origin. The multivariate analysis showed that CEA, p16 and MCM2 were the strongest predictors of site of origin. In the evaluation of six panels built by various combinations of immunomarkers , the panel with the lowest accuracy was that represented by MCM2, bcl2 and villin. The villin did not show any statistically significant difference in the differential diagnosis of these adenocarcinomas. Despite the MCM2 and bcl2 have revealed significant differences of frequency between the two sites of origin, they did not demonstrate additional benefit when added to a traditional panel. Conclusion: According to our study, the inclusion of MCM2, bcl2 and villin in the immunohistochemical assessment of uterine adenocarcinomas, added no supplementary value in the differentiation of these two neoplasms. / Adenocarcinomas endocervicais e endometriais são neoplasias uterinas com comportamentos biológicos e tratamentos distintos, sendo todo o plano terapêutico baseado no sítio de origem desses tumores. Para diferenciação dessas duas neoplasias, muitas vezes utiliza-se o estudo imuno-histoquímico como ferramenta auxiliar e complementar ao exame histopatológico. Prévios estudos têm investigado o valor de diferentes marcadores na distinção dessas neoplasias, com resultados variáveis e, por vezes, conflitantes. Neste estudo foi avaliado o desempenho dos marcadores MCM2, bcl2 e vilina no diagnóstico diferencial desses adenocarcinomas, associados ou não a um painel de marcadores tradicionais formados por CEA, vimentina, RE, RP e p16. Material e métodos: Um microarranjo de tecido (TMA) foi construído usando tecidos fixados em formol e embebidos em parafina, a partir de 104 amostras provenientes de histerectomias e conizações. Das 104 amostras, 51 eram representadas por casos inequívocos de adenocarcinomas de endocérvice e 53 representavam casos inequívocos de adenocarcinomas de endométrio. As secções do bloco de TMA foram imunomarcadas com os oito anticorpos em estudo e para vizualização da reação antígeno-anticorpo foi utilizado o sistema de detecção com polímeros. A marcação imuno-histoquímica foi graduada de acordo com o sistema semi-quantitativo alemão, levando-se em consideração a intensidade de marcação e a extensão de células marcadas. O score de imunorreatividade final foi determinado pela multiplicação da intensidade pela extensão de marcação. Um limite de corte de 4 foi determinado para diferenciação entre um resultado final positivo ou negativo (0- 3= negativo; 4- 12= positivo). Resultados: Análise univariada mostrou que dos oito marcadores avaliados, sete (CEA, vimentina, RE, RP, p16, MCM2 e bcl2) apresentaram bom desempenho na distinção entre origens endocervical e endometrial da neoplasia. Análise multivariada mostrou que CEA, p16 e MCM2 foram os mais fortes preditores do sítio anatômico. Na avaliação dos seis painéis construídos por combinações variadas desses marcadores, o painel com menor acurácia diagnóstica foi o representado por MCM2, bcl2 e vilina. A vilina não apresentou nenhuma diferença estatisticamente significativa no diagnóstico diferencial desses adenocarcinomas. Apesar do MCM2 e bcl2 terem revelado diferenças significativas de frequência entre os dois sítios de origem, eles não demonstraram valor suplementar quando adicionados a um painel tradicional. Conclusão: De acordo com este estudo, a inclusão de MCM2, bcl2 e vilina em um painel tradicional de 5 marcadores (CEA, vimentina, RE, RP, p16), não agregou nenhum benefício adicional na distinção imuno-histoquímica do sítio de origem desses adenocarcinomas uterinos.
Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.bc.ufg.br:tede/3201 |
Date | 16 October 2013 |
Creators | Cysneiros, Maria Auxiliadora de Paula Carneiro |
Contributors | Moreira, Marise Amaral Rebouças, Moreira, Marise Amaral Rebouças, Alves, Rosane R. Figueiredo, Zapata, Marco Túlio Garcia, Deus, José Miguel de |
Publisher | Universidade Federal de Goiás, Programa de Pós-graduação em Ciências da Saúde (FM), UFG, Brasil, Faculdade de Medicina - FM (RG) |
Source Sets | IBICT Brazilian ETDs |
Language | Portuguese |
Detected Language | Portuguese |
Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
Format | application/pdf |
Source | reponame:Biblioteca Digital de Teses e Dissertações da UFG, instname:Universidade Federal de Goiás, instacron:UFG |
Rights | http://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess |
Relation | -1006864312617745310, 600, 600, 600, 1545772475950486338, 7337577453819502453, ABU BACKER, F. M.; MUSTAPHA, N. R.; OTHMAN, N. H. Combined expression of p161NK4a and p27Kip1, but not p21WAF1, differentiates endocervical from endometrial adenocarcinoma. Anal Quant Cytol Histol, v. 33, n. 5, p. 283-8, Oct 2011. ALKUSHI, A. et al. Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray. Virchows Arch, v. 442, n. 3, p. 271-7, Mar 2003. ANSARI-LARI, M. A. et al. Distinction of endocervical and endometrial adenocarcinomas: immunohistochemical p16 expression correlated with human papillomavirus (HPV) DNA detection. Am J Surg Pathol, v. 28, n. 2, p. 160-7, Feb 2004. CAMERON, R. I. et al. Immunohistochemical staining with MIB1, bcl2 and p16 assists in the distinction of cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia. Histopathology, v. 41, n. 4, p. 313-21, Oct 2002. CASTRILLON, D. H.; LEE, K. R.; NUCCI, M. R. Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study. Int J Gynecol Pathol, v. 21, n. 1, p. 4-10, Jan 2002. CONESA-ZAMORA, P. et al. Effect of human papillomavirus on cell cycle-related proteins p16, Ki-67, Cyclin D1, p53, and ProEx C in precursor lesions of cervical carcinoma: a tissue microarray study. Am J Clin Pathol, v. 132, n. 3, p. 378-90, Sep 2009. DABBS, D. J.; STURTZ, K.; ZAINO, R. J. The immunohistochemical discrimination of endometrioid adenocarcinomas. Hum Pathol, v. 27, n. 2, p. 172-7, Feb 1996. Referências 38 EL-GHOBASHY, A. A. et al. Differential expression of cyclin-dependent kinase inhibitors and apoptosis-related proteins in endocervical lesions. Eur J Cancer, v. 43, n. 13, p. 2011-8, Sep 2007. HAN, C. P. et al. Scoring of p16(INK4a) immunohistochemistry based on independent nuclear staining alone can sufficiently distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study. Mod Pathol, v. 22, n. 6, p. 797-806, Jun 2009. HAN, C. P. et al. Adding the p16(INK4a) marker to the traditional 3-marker (ER/Vim/CEA) panel engenders no supplemental benefit in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray study. Int J Gynecol Pathol, v. 28, n. 5, p. 489-96, Sep 2009. HAN, C. P. et al. A reappraisal of three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR), and five-marker (ER/Vim/CEA/PR/p16INK4a) panels in the diagnostic distinction between primary endocervical and endometrial adenocarcinomas in a tissue microarray study. Arch Gynecol Obstet, v. 281, n. 5, p. 845-50, May 2010. IWAKAWA, M. et al. The radiation-induced cell-death signaling pathway is activated by concurrent use of cisplatin in sequential biopsy specimens from patients with cervical cancer. Cancer Biol Ther, v. 6, n. 6, p. 905-11, Jun 2007. JONES, M. W. et al. Immunohistochemistry and HPV in situ hybridization in pathologic distinction between endocervical and endometrial adenocarcinoma: a comparative tissue microarray study of 76 tumors. Int J Gynecol Cancer, v. 23, n. 2, p. 380-4, Feb 2013. KALOGIANNIDIS, I. et al. Immunohistochemical bcl-2 expression, p53 overexpression, PR and ER status in endometrial carcinoma and survival outcomes. Eur J Gynaecol Oncol, v. 29, n. 1, p. 19-25, 2008. Referências 39 KAMOI, S. et al. Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: another viewpoint. Int J Gynecol Pathol, v. 21, n. 3, p. 217-23, Jul 2002. KATO, K. et al. Expression of replication-licensing factors MCM2 and MCM3 in normal, hyperplastic, and carcinomatous endometrium: correlation with expression of Ki-67 and estrogen and progesterone receptors. Int J Gynecol Pathol, v. 22, n. 4, p. 334-40, Oct 2003. KOK, L. F. et al. Comparing the scoring mechanisms of p16INK4a immunohistochemistry based on independent nucleic stains and independent cytoplasmic stains in distinguishing between endocervical and endometrial adenocarcinomas in a tissue microarray study. Arch Gynecol Obstet, v. 281, n. 2, p. 293-300, Feb 2010. KONG, C. S.; BECK, A. H.; LONGACRE, T. A. A panel of 3 markers including p16, ProExC, or HPV ISH is optimal for distinguishing between primary endometrial and endocervical adenocarcinomas. Am J Surg Pathol, v. 34, n. 7, p. 915-26, Jul 2010. KOO, C. L. et al. Scoring mechanisms of p16INK4a immunohistochemistry based on either independent nucleic stain or mixed cytoplasmic with nucleic expression can significantly signal to distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study. J Transl Med, v. 7, p. 25, 2009. LIANG, J. et al. Utility of p16INK4a, CEA, Ki67, P53 and ER/PR in the differential diagnosis of benign, premalignant, and malignant glandular lesions of the uterine cervix and their relationship with Silverberg scoring system for endocervical glandular lesions. Int J Gynecol Pathol, v. 26, n. 1, p. 71-5, Jan 2007. MATOS, L. L. et al. Immunohistochemistry quantification by a digital computer-assisted method compared to semiquantitative analysis. Clinics (Sao Paulo), v. 61, n. 5, p. 417-24, Oct 2006. MCCLUGGAGE, W. G. Immunohistochemistry as a diagnostic aid in cervical pathology. Pathology, v. 39, n. 1, p. 97-111, Feb 2007. Referências 40 MCCLUGGAGE, W. G.; JENKINS, D. p16 immunoreactivity may assist in the distinction between endometrial and endocervical adenocarcinoma. Int J Gynecol Pathol, v. 22, n. 3, p. 231-5, Jul 2003. MCCLUGGAGE, W. G. et al. A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol, v. 21, n. 1, p. 11-5, Jan 2002. NAKAMURA, E. et al. Villin1, a novel diagnostic marker for cervical adenocarcinoma. Cancer Biol Ther, v. 8, n. 12, p. 1146-53, Jun 2009. O'NEILL, C. J.; MCCLUGGAGE, W. G. p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol, v. 13, n. 1, p. 8-15, Jan 2006. RAO, P. H. et al. Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma. BMC Cancer, v. 4, p. 5, Feb 6 2004. STAEBLER, A. et al. Hormone receptor immunohistochemistry and human papillomavirus in situ hybridization are useful for distinguishing endocervical and endometrial adenocarcinomas. Am J Surg Pathol, v. 26, n. 8, p. 998-1006, Aug 2002. YAO, C. C. et al. Ancillary p16(INK4a) adds no meaningful value to the performance of ER/PR/Vim/CEA panel in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray study. Arch Gynecol Obstet, v. 280, n. 3, p. 405-13, Sep 2009. YEMELYANOVA, A. et al. Utility of p16 expression for distinction of uterine serous carcinomas from endometrial endometrioid and endocervical adenocarcinomas: immunohistochemical analysis of 201 cases. Am J Surg Pathol, v. 33, n. 10, p. 1504-14, Oct 2009. |
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