SFRP1, Posible biomarcador en la progresión o regresión de lesiones de cérvix asociado al Virus del Papiloma Humano / SFRP1, Possible Biomarker in the Progression or Regression of Cervical Pre-neoplastic Lesions Associated with Human Papilloma Virus

Resumen Objetivo: Comparar la expresión de mRNA y proteínas de SFRP1, PTPRN, CDO1, EDNRB, CDX2, EPB41L3 y HAND1 en pacientes con lesión intra-epitelial cervical de bajo y alto grado, con posterior progresión o regresión. Material y Método: Se realizó análisis de expresión de genes mediante RT-PCR y análisis de expresión de proteínas por inmunohistoquímica. El análisis estadís tico fue realizado con las pruebas: Wilcoxon, coeficiente de correlación de Spearman e índice de concordancia. Las muestras fueron pareadas en momento 1 y momento 2. Resultados: SFRP1 mostró tendencia de mayor expresión de mRNA en lesión intra-epitelial de bajo grado (momento 2) Vs. alto grado (momento 1). La expresión de proteínas por inmunohistoquímica de SFRP1 en casos de progresión (83,3 %) mostró disminución en su graduación (p = 0,0313*); los demás genes en estudio no tuvieron cambios estadísticamente significativos. Discusión: SFRP1 mostró comportamiento ajustado a resultados de estudios previos donde se encontró hipermetilado en lesiones intra-epiteliales de alto grado; su subexpresión por hipermetilación se reportó en otros canceres, proceso que colabora con su silenciamiento y transición epitelial-mesenquimatosa del cáncer de cuello uterino. Conclusiones. SFRP1 es potencial biomarcador en lesiones preneoplásicas del cuello uterino asociadas al virus de papiloma humano.

Abstract Objective. The aim of this work was to compare the expression of mRNA and proteins of SFRP1, PTPRN, CDO1, EDNRB, CDX2, EPB41L3 and HAND1 in patients with low and high grade cervical intraepithelial lesion, with subsequent progression or regression. Material and Methods: Gene expression analysis was conducted through RT-PCR and protein expression analysis was performed by immunohistochemistry. The statistics analysis were Wilcoxon test, Spearman's correlation coefficient and concordance index. The samples were paired during moment 1 (initial patient diag nosis) and moment 2 (follow-up histological diagnosis). Results: SFRP1 showed a trend of higher mRNA expression in low-grade intra-epithelial lesions (moment 2) Vs. high-grade (moment 1). The expression of proteins by immunohistochemistry of SFRP1 in progression cases (83.3%) showed a decrease in its graduation (p = 0.0313*); the other genes under study had no statistically significant. Discussion: SFRP1 showed a biological behavior adjusted to the results of previous studies where hypermethylation was found in high-grade intra-epithelial lesions; its subexpression by hypermethylation has been reported in other cancers, a process that collaborates with its silencing and epithelial-mesenchymal tran sition of cervical. Conclusions. SFRP1 is a potential biomarker in preneoplastic lesions of the cervix associated with human papillomavirus.

In situ growth in early lung adenocarcinoma may represent precursor growth or invasive clone outgrowth-a clinically relevant distinction.

The switch from in situ to invasive tumor growth represents a crucial stage in the evolution of lung adenocarcinoma. However, the biological understanding of this shift is limited, and 'Noguchi Type C' tumors, being early lung adenocarcinomas with mixed in situ and invasive growth, represent those that are highly valuable in advancing our understanding of this process. All Noguchi Type C adenocarcinomas (n = 110) from the LATTICE-A cohort were reviewed and two patterns of in situ tumor growth were identified: those deemed likely to represent a true shift from precursor in situ to invasive disease ('Noguchi C1') and those in which the lepidic component appeared to represent outgrowth of the invasive tumor along existing airspaces ('Noguchi C2'). Overall Ki67 fraction was greater in C2 tumors and only C1 tumors showed significant increasing Ki67 from in situ to invasive disease. P53 positivity was acquired from in situ to invasive disease in C1 tumors but both components were positive in C2 tumors. Likewise, vimentin expression was increased from in situ to invasive tumor in C1 tumors only. Targeted next generation sequencing of 18 C1 tumors identified four mutations private to the invasive regions, including two in TP53, while 6 C2 tumors showed no private mutations. In the full LATTICe-A cohort, Ki67 fraction classified as either less than or greater than 10% within the in situ component of lung adenocarcinoma was identified as a strong predictor of patient outcome. This supports the proposition that tumors of all stages that have 'high grade' in situ components represent those with aggressive lepidic growth of the invasive clone. Overall these data support that the combined growth of Noguchi C tumors can represent two differing biological states and that 'Noguchi C1' tumors represent the genuine biological shift from in situ to invasive disease.

Experiencia del Laboratorio Central de Citopatología de la Secretaría Distrital de Salud de Bogotá, D. C, durante su primer año de funcionamiento / Experience of the Central Cytopathology Laboratory of the Secretaría Distrital de Salud de Bogotá, D. C., during its first year of operation

La Secretaría Distrital de Salud de Bogotá, luego de analizar los problemas de baja cobertura del programa de prevención y detección precoz del cáncer cérvico uterino, inoportunidad en la entrega de los resultados de la lectura de citología vaginal y falta de procesos estructurados e implementados para el control de calidad interno y externo por parte de los hospitales públicos de la red adscrita, diseñó y organizó el Laboratorio Central de Citopatología (LCC) a partir del 1° de septiembre de 2002, a través de un convenio interadministrativo con los hospitales de la red adscrita de III nivel y uno de II nivel. En el primer año de funcionamiento se procesaron y analizaron 154.708 muestras de citología vaginal, para un incremento en la cobertura anual del programa del 157,85%. Se mejoró la oportunidad en la entrega de los resultados (promedio 8,7 días), calidad en la toma de las muestras y se instauraron los procesos para el control interno y externo de calidad con el fin de garantizar diagnósticos citopatológicos confiables. En conclusión, la centralización del procesamiento y lectura de citología vaginal por el LCC, impactó positivamente durante su primer año de actividades en la ampliación de cobertura en toma y lectura de citología vaginal, mejoramiento en la calidad de la toma de muestras por los hospitales, pertinencia en el diagnóstico crtopatológico, oportunidad en la entrega de resultados y seguimiento de las pacientes a través de la base de datos del laboratorio.

The District Health Secretariat of Bogota, after analyzing the problems of low coverage of the cervical uterine cancer prevention and early detection program, untimeliness in the delivery of Pap smear reading results and lack of structured and implemented processes for internal and external quality control by the public hospitals of the affiliated network, designed and organized the Central Cytopathology Laboratory (LCC) as of September 1, 2002, through an inter-administrative agreement with the hospitals of the affiliated network, designed and organized the Central Cytopathology Laboratory (CCL) as of September 1, 2002, through an inter-administrative agreement with the hospitals of the affiliated III level network and one of II level. In the first year of operation, 154,708 vaginal cytology samples were processed and analyzed, for an increase in the program's annual coverage of 157.85%. The timeliness of results delivery was improved (average 8.7 days), the quality of sample collection was improved, and internal and external quality control processes were implemented to ensure reliable cytopathological diagnoses. In conclusion, the centralization of the processing and reading of vaginal cytology by the LCC had a positive impact during its first year of activities on the expansion of coverage in the collection and reading of vaginal cytology, improvement in the quality of sample collection by the hospitals, relevance in the crtopathological diagnosis, timeliness in the delivery of results and follow-up of patients through the laboratory's database.