RESUMO
The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre-and postmenopausal, were included consecutively in a prospective and observational follow-up study. Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients' age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considering risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Endométrio/efeitos dos fármacos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/efeitos adversos , Doenças Uterinas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Endométrio/patologia , Feminino , Seguimentos , Humanos , Histeroscopia , Pessoa de Meia-Idade , Pólipos/induzido quimicamente , Pólipos/diagnóstico , Pólipos/patologia , Pós-Menopausa , Estudos Prospectivos , Doenças Uterinas/induzido quimicamente , Doenças Uterinas/diagnósticoRESUMO
Los objetivos fueron evaluar la prevalencia de afecciones endometriales en pacientes tratadas con tamoxifeno (TAM) y analizar los aspectos epidemiológicos, ecográficos, histeroscópicos e histopatológicos. Desde enero de 1999 a diciembre 2008 se estudiaron 152 pacientes con cáncer de mama tratadas con TAM (20 mg/día), sintomáticas (con sangrado) o asintomáticas, pre y postmenopáusicas, incluidas en forma consecutiva. El diseño fue prospectivo y observacional. Los métodos diagnósticos usados fueron ecografía transvaginal, histeroscopía y biopsia. Las pacientes fueron seguidas durante 5 años con ecografía cada 12 meses e histeroscopia con biopsia en casos que lo justificaran. Edad: 62.76 ± 10.24 años y tiempo de tratamiento: 36.2 ± 19.9 meses. El adenocarcinoma se observó en 3/87 (3.45%) pacientes con factores de riesgo y en 1/65 (1.54%) sin ellos (RA: 1.91, IC 95% 1.88 a 1.94). Las afecciones benignas se hallaron en 148 pacientes (97.37% y los adenocarcinomas en 4 (2.63%),1 en un pólipo de aspecto benigno. Los 4 se observaron en mujeres postmenopáusicas (2 asintomáticas) con grosor endometrial igual o mayor a 16 mm. El riesgo de cáncer fue significativamente mayor en sintomáticas (2.36 versus 0.42 en asintomáticas). Tres adenocarcinomas se detectaron entre 24 y 48 meses del tratamiento. Recomendamos un seguimiento con ecografía transvaginal de las pacientes asintomáticas, resección de los pólipos evaluando factores de riesgo y tiempo de exposición, en especial luego de los 24 meses. Consideramos aceptable un cut-off = 10 mm en el grosor del endometrio en postmenopáusicas asintomáticas para realizar histeroscopía y biopsia.
The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre- and postmenopausal, were included consecutively in a prospective and observational follow-up study Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients´ age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considerin risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adenocarcinoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Endométrio/efeitos dos fármacos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/efeitos adversos , Doenças Uterinas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Biópsia , Endométrio/patologia , Seguimentos , Histeroscopia , Pós-Menopausa , Estudos Prospectivos , Pólipos/induzido quimicamente , Pólipos/diagnóstico , Pólipos/patologia , Doenças Uterinas/induzido quimicamente , Doenças Uterinas/diagnósticoRESUMO
Los objetivos fueron evaluar la prevalencia de afecciones endometriales en pacientes tratadas con tamoxifeno (TAM) y analizar los aspectos epidemiológicos, ecográficos, histeroscópicos e histopatológicos. Desde enero de 1999 a diciembre 2008 se estudiaron 152 pacientes con cáncer de mama tratadas con TAM (20 mg/día), sintomáticas (con sangrado) o asintomáticas, pre y postmenopáusicas, incluidas en forma consecutiva. El diseño fue prospectivo y observacional. Los métodos diagnósticos usados fueron ecografía transvaginal, histeroscopía y biopsia. Las pacientes fueron seguidas durante 5 años con ecografía cada 12 meses e histeroscopia con biopsia en casos que lo justificaran. Edad: 62.76 ± 10.24 años y tiempo de tratamiento: 36.2 ± 19.9 meses. El adenocarcinoma se observó en 3/87 (3.45%) pacientes con factores de riesgo y en 1/65 (1.54%) sin ellos (RA: 1.91, IC 95% 1.88 a 1.94). Las afecciones benignas se hallaron en 148 pacientes (97.37% y los adenocarcinomas en 4 (2.63%),1 en un pólipo de aspecto benigno. Los 4 se observaron en mujeres postmenopáusicas (2 asintomáticas) con grosor endometrial igual o mayor a 16 mm. El riesgo de cáncer fue significativamente mayor en sintomáticas (2.36 versus 0.42 en asintomáticas). Tres adenocarcinomas se detectaron entre 24 y 48 meses del tratamiento. Recomendamos un seguimiento con ecografía transvaginal de las pacientes asintomáticas, resección de los pólipos evaluando factores de riesgo y tiempo de exposición, en especial luego de los 24 meses. Consideramos aceptable un cut-off = 10 mm en el grosor del endometrio en postmenopáusicas asintomáticas para realizar histeroscopía y biopsia.(AU)
The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre- and postmenopausal, were included consecutively in a prospective and observational follow-up study Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients´ age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considerin risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.(AU)
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adenocarcinoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Endométrio/efeitos dos fármacos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/efeitos adversos , Doenças Uterinas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Biópsia , Endométrio/patologia , Seguimentos , Histeroscopia , Pólipos/induzido quimicamente , Pólipos/diagnóstico , Pólipos/patologia , Pós-Menopausa , Estudos Prospectivos , Doenças Uterinas/induzido quimicamente , Doenças Uterinas/diagnósticoRESUMO
The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre-and postmenopausal, were included consecutively in a prospective and observational follow-up study. Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45
) with risk factors and in 1/65 (1.54
) without them (RA 1.91, IC 95
1.88-1.94). We found benign disease in 148 patients (97.37
) and adenocarcinomas in 4 (2.63
), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considering risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Endométrio/efeitos dos fármacos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/efeitos adversos , Doenças Uterinas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Endométrio/patologia , Feminino , Seguimentos , Humanos , Histeroscopia , Pessoa de Meia-Idade , Pólipos/induzido quimicamente , Pólipos/diagnóstico , Pólipos/patologia , Pós-Menopausa , Estudos Prospectivos , Doenças Uterinas/induzido quimicamente , Doenças Uterinas/diagnósticoRESUMO
The metastasis status of pelvic lymph nodes (PLNs) seems to be a predictive factor of survival. It was suggested that the presence of HPV DNA and other biological markers in PLN may indicate a sub clinical early metastasis. The aim was to describe the prevalence and distribution patterns of HPV DNA and H-ras mutations in intra operatively obtained cervical tumors and PLN. Thirty-seven cervical tumors and 61 lymph node biopsies from 37 patients with cervical cancer were selected. HPV typing and location were performed by PCR/dot blot and in situ hybridization (ISH) respectively. PCR/RFLP was used to scan for mutations in H-ras. Hundred percent of the cervical cancers and 85% of the PLN were HPV positive; co-infection with more than one type was 27%. HPV 16 was detected alone or co-infecting with other types in 84% of tumors and 46% of PLN; the second most frequent viral type was HPV 18 (tumor: 27%; PLN: 20%). In PLN, HPV was located in nuclei or/and cytoplasm of lymphocytes, macrophages, endothelial, and /or stromal cells. H-ras mutations were identified in 5/24 (21%) of patients with cervical tumors showing poor or moderated differentiation. HPV DNA in histological tumor-free PLN not necessary indicate metastasis, but it may be associated to an active immune reaction. Mutated H-ras is probably involved in cervical carcinogenesis and its detection in tumor and metastasis free PLN may be related to early metastasis or recurrence in at least a subset of poorly differentiated cervical tumors.
Assuntos
Genes ras , Linfonodos/virologia , Mutação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Núcleo Celular/virologia , Citoplasma/virologia , DNA Viral/genética , Células Endoteliais/virologia , Feminino , Seguimentos , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Hibridização In Situ , Linfócitos/virologia , Macrófagos/virologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Estudos Retrospectivos , Células Estromais/virologiaRESUMO
BACKGROUND: Epidemiological and virological surveys suggest that the HPV presence is not enough condition to generate anogenital cancer, others factors (genetic, environmental, hormonal, etc) may have an important role. Mutations of ras genes were observed in several human neoplasias, including cervical cancer. OBJECTIVE: The aim of the study was to assess the frequency of Ha-ras oncogene mutations in cervical intraepithelial neoplasia (CIN) grade III and invasive squamous cell carcinomas and to examine this genetic factor in relation to HPV infection and the clinical evolution of cervical lesions. STUDY DESIGN: They were selected for (a) evaluation of the frequency of Ha-ras mutations: 39 cases of invasive carcinomas (InCa), 47 CIN III and 12 normal tissues taken from areas adjacent to the tumor (NT). (b) Retrospective follow-up: 18 cases of lesion progression; 9 cases of persistence and 12 of regression to mature or immature metaplasia after specific treatment. All biopsies obtained from each patient during the follow-up done between 5 and 10 years were included. HPV typing and scanning of possible mutations in Ha-ras were made by single-strand conformation polymorphism analysis/polymerase chain reaction. RESULTS: HPV-DNA was detected in 95% of InCa and 84% of CIN III; HPV 16/18 was found in 65% of patients, mainly associated with persistent infection and lesion progression. The undetermined HPV types (18%) could indicate the circulation in our country of types other than those screened (6, 11, 16, 18, 31 and 33). Twenty percent of CIN III and 41% of InCa had patterns compatible with Ha-ras mutations. Mutated Ha-ras was detected in 61 and 44% of progression and persistence cases, respectively, including early stages of progression. CONCLUSIONS: Ha-ras mutations were detected in CIN II-III lesions; in mutated cases, the progression took place in under 2 years, then this detection may be an early predictive marker of rapid progression.
Assuntos
Genes ras/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Colo do Útero/patologia , Colo do Útero/virologia , Progressão da Doença , Feminino , Humanos , Papillomaviridae/classificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
The aim of this study w trial randomized as to investigate the frequencies of human papillomavirus (HPV) and mutation in Ha-ras oncogene and tumour suppressor p53 gene in cervical cancer and precursor lesions. A total of 30 invasive carcinomas (IC), 36 cervical intraepithelial neoplasia grade III (CIN III) and 12 normal tissues adjacent to the tumor (NT) were included. HPV typification and scanning of possible mutations in Ha-ras and p 53 genes were made by SSCP-PCR. The IC cases showed 93 HPV positivity, 41 having mobility shifts for Ha-ras mutations and 17 for p53 mutations while in CIN III, these percentages were 80, 18 and 11, respectively. In normal tissues HPV frequency was 17. All Ha-ras mutated samples were HPV positive but 33 of p53 mutated cases were HPV negative. All mutations were heterozygous. HPV 16 was more prevalent (44) than HPV 18 (15) and the high rate of undetermined HPV types (18) would indicate the circulation in our country of other types different from the assayed HPV controls (6, 11, 16, 18, 31 and 33), being variants or mixed infections. The low frequency of p53 mutations (17) strengthens the view that wild type p53 inactivation by HPV probably plays a major role in the pathogenesis of cervical cancer. Because mutated Ha-ras was found in HPV associated premalignant lesions, we speculate that it represents an early marker for progression. Our findings provide additional evidence for an interactive effect between high risk types of HPV and oncogene activation in the development of uterine cervical cancer.(Au)
Assuntos
Humanos , Feminino , RESEARCH SUPPORT, NON-U.S. GOVT , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Genes p53/genética , Genes ras/genética , Papillomavirus Humano/genética , /virologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/genética , DNA Viral/genética , Mutação/genética , /genética , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita SimplesRESUMO
El objetivo del estudio fue investigar las frecuencias de virus papiloma humano (HPV) y de mutaciones en los genes Ha-ras y el supresor p53 en tumores y lesiones precursoras de cérvix. Se incluyeron en el estudio 30 carcinomas invasores (CAIN), 36 displasias severas (CIN III) y 12 tejidos normales adyacentes a los tumores (TN). Se realizó la tipificación de HPV y la búsqueda de mutaciones en los genes Ha-ras y p 53 mediante PCR-SSCP. Los CAIN fueron HPV positivos en el 93%; en el 41% se observaron mutaciones en Ha-ras y en el 17% para p53. El 80% de los CIN III fue HPV positivo, en el 18% se detectaron mutaciones en Ha-ras y en el 11% en p53. En los TN el HPV se detectó en el 17% de los casos. Todas las mutaciones fueron heterocigotas. Por otro lado, todas las muestras con mutaciones en Ha-ras resultaron HPV positivas, en cambio el 33% de los casos de p53 mutada fueron HPV negativos. El HPV 16 (44%) fue más prevalente que el HPV 18 (15%); los casos de tipo viral no determinado (18%), indicarían la circulación en nuestro país, de otros tipos distintos a los ensayados (6, 11, 16, 18, 31 y 33), variantes o infecciones mixtas. La baja frecuencia de mutaciones en el gen p53 señala que la inactivación de la proteína normal mediada por HPV tendría un rol más importante en la patogénesis del cáncer. Dado que el Ha-ras mutado se halló en lesiones premalignas, hemos especulado que podría representar un marcador temprano de progresión. Nuestros hallazgos proveen de evidencias adicionales acerca de un efecto interactivo entre los HPV de alto riesgo y de oncogenes en el desarrollo tumoral.
Assuntos
Humanos , Feminino , Genes p53 , Genes ras , Papillomaviridae , Infecções por Papillomavirus , Infecções Tumorais por Vírus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , DNA Viral , Mutação , Infecções por Papillomavirus , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Infecções Tumorais por Vírus , Displasia do Colo do Útero , Neoplasias do Colo do ÚteroRESUMO
El objetivo del estudio fue investigar las frecuencias de virus papiloma humano (HPV) y de mutaciones en los genes Ha-ras y el supresor p53 en tumores y lesiones precursoras de cérvix. Se incluyeron en el estudio 30 carcinomas invasores (CAIN), 36 displasias severas (CIN III) y 12 tejidos normales adyacentes a los tumores (TN). Se realizó la tipificación de HPV y la búsqueda de mutaciones en los genes Ha-ras y p 53 mediante PCR-SSCP. Los CAIN fueron HPV positivos en el 93%; en el 41% se observaron mutaciones en Ha-ras y en el 17% para p53. El 80% de los CIN III fue HPV positivo, en el 18% se detectaron mutaciones en Ha-ras y en el 11% en p53. En los TN el HPV se detectó en el 17% de los casos. Todas las mutaciones fueron heterocigotas. Por otro lado, todas las muestras con mutaciones en Ha-ras resultaron HPV positivas, en cambio el 33% de los casos de p53 mutada fueron HPV negativos. El HPV 16 (44%) fue más prevalente que el HPV 18 (15%); los casos de tipo viral no determinado (18%), indicarían la circulación en nuestro país, de otros tipos distintos a los ensayados (6, 11, 16, 18, 31 y 33), variantes o infecciones mixtas. La baja frecuencia de mutaciones en el gen p53 señala que la inactivación de la proteína normal mediada por HPV tendría un rol más importante en la patogénesis del cáncer. Dado que el Ha-ras mutado se halló en lesiones premalignas, hemos especulado que podría representar un marcador temprano de progresión. Nuestros hallazgos proveen de evidencias adicionales acerca de un efecto interactivo entre los HPV de alto riesgo y de oncogenes en el desarrollo tumoral. (AU)