Overexpression of p53 protein is a marker of poor prognosis in Mexican women with breast cancer.

Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase 2α (TOP2α) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2α genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102 biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2α gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2α and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50 years, and Scarff-Bloom-Richardson (SBR) histological grade III (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2α were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2α amplification and overexpression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.

Survival and risk of relapse of acute lymphoblastic leukemia in a Mexican population is affected by dihydrofolate reductase gene polymorphisms.

Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. Polymorphisms in the gene coding for DHFR have been associated with adverse event treatment. This study evaluated the effect of the -A317G and C829T polymorphisms in the DHFR gene on survival and risk of relapse of ALL. Seventy patients with ALL and 100 healthy individuals were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. An association between the polymorphisms and the risk of relapse was found (p<0.05); patients with the -317G/G genotype were found to have an 8.55 (95% CI 1.84-39.70) higher chance of relapse and carriers of the 829T/T genotype had a 14.0 (95% CI 1.13-172.63) higher chance of relapse. Other variables, such as age and leukocyte count, were associated (p<0.05) with the risk of relapse of the disease. Individuals with the G/G and T/T genotype of the -A317G and C829T polymorphisms had poorer survival compared to other genotype groups (log-rank test; p<0.05). Although preliminary, these data seem to suggest a role for the DHFR polymorphisms in the risk of relapse of ALL and the mortality risk in these patients.

Polymorphisms of the gamma-glutamyl hydrolase gene and risk of relapse to acute lymphoblastic leukemia in Mexico.

This study evaluated the association of -401C/T and +452C/T polymorphisms of gamma-glutamyl hydrolase and the risk of relapse to acute lymphoblastic leukemia. Genotyping was performed in 70 children with acute lymphoblastic leukemia and 140 healthy children. An association between the -401C/T polymorphism and the risk of relapse was found (p=0.028), patients with the -401T/T genotype have 10.83 (95% CI 1.30-90.14) more chance of a relapse of leukemia. No association was found between the +452C/T polymorphism and the risk of relapse. Therefore, our investigation suggests that the -401C/T polymorphism in the gamma-glutamyl hydrolase may be a factor involved in the generation of relapse to disease in patients with ALL.

AgNOR polymorphism association with squamous intraepithelial lesions and invasive carcinoma with HPV infection.

OBJECTIVE: Evaluate the relationships between AgNORs polymorphisms and squamous intraepithelial lesions (SIL) and squamous cell carcinoma (SCC) with HPV infection. MATERIALS AND METHODS: A study was carried out on sixty women from the state of Guerrero, Mexico. HPV detection was performed by PCR. AgNORs were identified by argentic impregnation. One hundred cells per slide were counted and classified according to the polymorphism of AgNORs dots; typical (spherical) and atypical (large, kidney-shaped and clustered). RESULTS: A total of 100% of the cases were positive for HPV infection. Nine different high-risk HPV genotypes were found, type 16 was the most common (48.6%). The AgNORs showed a significant decrease in spherical shape according to neoplastic development. The three atypical shapes showed a significant increase in SIL and SCC (p-trend<0.001). CONCLUSIONS: AgNORs polymorphism rises progressively according to the grade of histological lesions that can be useful as a prognosis for progression of SCC.

AgNOR polymorphism association with squamous intraepithelial lesions and invasive carcinoma with HPV infection / Asociación de los polimorfismos AgNORs con lesiones intraepiteliales escamosas, carcinoma cervical e infección por VPH

OBJECTIVE: Evaluate the relationships between AgNORs polymorphisms and squamous intraepithelial lesions (SIL) and squamous cell carcinoma (SCC) with HPV infection. MATERIALS AND METHODS: A study was carried out on sixty women from the state of Guerrero, Mexico. HPV detection was performed by PCR. AgNORs were identified by argentic impregnation. One hundred cells per slide were counted and classified according to the polymorphism of AgNORs dots; typical (spherical) and atypical (large, kidney-shaped and clustered). RESULTS: A total of 100 percent of the cases were positive for HPV infection. Nine different high-risk HPV genotypes were found, type16 was the most common (48.6 percent). The AgNORs showed a significant decrease in spherical shape according to neoplastic development. The three atypical shapes showed a significant increase in SIL and SCC (p-trend<0.001). CONCLUSIONS: AgNORs polymorphism rises progressively according to the grade of histological lesions that can be useful as a prognosis for progression of SCC.

OBJETIVO: Evaluar la relación entre los polimorfismos de AgNORs con las lesiones intraepiteliales escamosas (LIE) y carcinoma de células escamosas (CCE). MATERIAL Y MÉTODOS: Se estudiaron sesenta mujeres del estado de Guerrero, México. La detección del VPH fue por PCR y los AgNORs por impregnación argéntica; se contaron 100 células y se clasificaron por tipo de polimorfismo de AgNORs: típico (esférico) y atípicos (largo, forma de riñón o de racimo). RESULTADOS: El 100 por ciento de los casos presentaron infección por VPH, se encontraron nueve genotipos diferentes de VPH de alto riesgo, el 16 fue el más común (48.6 por ciento). La forma esférica de los polimorfismos de AgNORs mostró una disminución con el desarrollo neoplásico y las atípicas incrementaron progresivamente con SIL y SCC (p-tendencia<0.001). CONCLUSIONES: Los polimorfismos AgNORs se incrementan progresivamente con el grado de lesión histológica, y pueden ser útiles en el pronóstico de progresión del carcinoma cervical.

Cervical carcinoma in Southern Mexico: Human papillomavirus and cofactors.

BACKGROUND: This study was conducted to determine human papillomavirus (HPV) types in women with cervical cancer (CC) and normal cervical cytology in the Southern region of Mexico, and to know the contribution of HPV types and cofactors in cervical cancer etiology. METHODS: A case-control study was performed in 133 women with CC and 256 controls. HPV detection was done by MY09/11 and GP5+/GP6+ PCR systems and typing by restriction fragment length polymorphism or DNA sequencing. RESULTS: HPV was found in 100% of CC and 35.5% of controls. The genotype distribution in CC was: HPV 16 (66.8%), 18 (9%), 31 (7.5%), 45 (4.5%), 58 (3.7%), 69 (3%), 52 (1.6%), 6, 11, 33, 56, and 67 (0.8% each). Among controls, HPV 33 followed by HPV 16 were the most frequent. Cervical cancer was associated with HPV 16 (OR=573.5), HPV 18 (OR=804.4), and undetermined risk HPV (types 67 and 69) (OR=434.3). Age at first intercourse <16 years (OR=9.6) and > or =3 births (OR=16) were significant risk factors for CC. CONCLUSIONS: HPV 16, by far, is the most frequent type in CC, HPV 16 and 18 are responsible for 75.8% of the CC cases and high-risk HPV for 94.7%, which is useful data to take into account in vaccination programs. HPV 33 is the most frequent type in controls and high-risk HPV are more common than low-risk HPV.

Experiencia con 14 casos de pseudoquiste pancreático / Experience with 14 cases of pancreatic pseudocyst

Introducción: el pseudoquiste de páncreas (PP) se presenta en 2 a 5 por ciento de los casos de pancreatitits aguda (PA). La mayoría se resuelve de forma espontánea. En hospitales oncológicos es una patología poco frecuente. Puede confundirse con neoplasias quísticas, motivo de envío a instituciones especializadas. Objetivo: describir los casos de PP tratados en un periodo de 15 años. Material y métodos: revisión de expedientes clínicos de 14 pacientes con diagnóstico de PP tratados desde 1975 hasta 1989. Resultados: nueve fueron mujeres (64 por ciento) y cinco fueron varones (36 por ciento). La edad promedio fue de 41 años (margen de 18 a 77). Hubo antecedente de alcoholismo intenso en 50 por ciento de los casos, litiasis vesicular en 28 por ciento y traumatismo en 15 por ciento. En cinco pacientes (35 por ciento) se documentó el antecedente de PA y el tiempo de evolución promedio entre ésta y el diagnóstico de PPe fue de 5.7 meses. En todos se presentó dolor y masa abdominal. El diagnóstico se realizó con ultrasonografía y tomografía en todos los casos. Fueron tratados quirúrgicamente trece casos, 12 con derivación interna, uno con resección y otro con drenaje externo que recurrió a los 16 meses. Se presentó fístula enterocutánea (7 por ciento) que fue resuelta médicamente. No se presentaron muertes operatorias. El tiempo de seguimiento promedio fue de 10 años 4 meses. Conclusiones: es una patología poco frecuente en hospitales oncológicos. El tratamiento quirúrgico más usado es drenaje interno. Se debe realizar diagnóstico diferencial con neoplasias quísticas de páncreas