Prognostic significance of tissue-type plasminogen activator (tPA) content in gastric cancer and surrounding mucosa.

AIMS: We analyzed the tPA content in primary gastric carcinomas and surrounding mucosa in order to assess the relationship between tPA content, clinicopathological tumor characteristics, and estrogen and progesterone receptor content. We evaluated the prognostic value of this serine protease in gastric cancer patients. PATIENTS AND METHODS: 122 resected gastric neoplasms and 95 adjacent mucosa samples were studied. The tPA content was measured in cytosol by an ELISA method. Cytosolic ER and PgR were measured with a solid phase enzyme immunoassay. RESULTS: Cytosolic tPA levels in neoplastic tissues (median 1.0 ng/mg prot) were significantly lower (p=0.002) than those found in paired mucosa samples (median 2.3 ng/mg prot). There was no significant association between tPA levels and clinicopathological parameters or PgR content, but tPA levels were significantly correlated with ER content. The intermediate-tPA-content group, corresponding to samples with between 0.3 and 1.70 ng/mg protein, proved to have a significantly high risk of relapse. CONCLUSIONS: We found a wide variability in tPA levels in gastric carcinoma and adjacent mucosa samples, with significantly decreased levels in tumors and a significantly positive relationship between tPA levels and ER status. There was a non-monotonic relationship between tPA levels and prognosis in patients with gastric cancer.

Expresión y significación clínica del pepsinógeno c y la colagenasa-3 en el carcinoma de endometrio / Expression and clinical significance of pepsinogen C and collagenase-3 in endometrial carcinoma

Objetivo: Analizar la expresión tumoral del pepsinógeno C y de la colagenasa-3 en el adenocarcinoma de endometrio y la relación con las características de las pacientes y de sus tumores.Sujetos y métodos: Analizamos retrospectivamente mediante análisis inmunohistoquímico, utilizando anticuerpos monoclonales, 58 pacientes diagnosticadas y tratadas de adenocarcinoma de endometrio.Resultados: Se detectó pepsinógeno C en 21 tumores (36 por ciento) y colagenasa-3 en 30 (51 por ciento). La expresión de estas proteínas se asoció significativamente con la profundidad de la invasión miometrial, de forma que a mayor invasión del miometrio, menor expresión de pepsinógeno C y mayor de colagenasa-3 (p < 0,005 y p < 0,02, respectivamente). El análisis combinado de ambas enzimas proteolíticas predijo significativamente el grado de invasión miometrial (p < 0,001).Conclusión: Un porcentaje significativo de adenocarcinomas de endometrio expresan pepsinógeno C y colagenasa-3, lo cual refleja un comportamiento biológico diferente, y pueden ser útiles en la predicción preoperatoria de la invasión miometrial en el cáncer de endometrio (AU)

[Analysis of the cytosolic content of the pS2 protein in breast cancer]. / Análisis del contenido citosólico de la proteína pS2 en el cáncer de mama.

OBJECTIVE: To analyze pS2 cytosolic levels in breast carcinomas and their correlation with different clinical characteristics of the patients and their tumours. MATERIAL AND METHODS: Cytosolic pS2 levels were measured by radioimmunometric assay in tumours from 168 breast cancer patients. RESULTS: The pS2 values ranged from 0 to 251 ng/mg protein (mean SD: 21.8 38.1; median: 7.9 ng/mg protein). These protein levels were significantly (p < 0.05) higher in premenopausal patients (27.6 45.2) than in postmenopausal patients (19.5 33.8). Intratumour pS2 levels were also significantly (p < 0.05) correlated with histologic grade of the tumours, and were higher in well diferentiated tumours (grade I: 28.8 42.8) than in moderately differentiated tumours (grade II: 19.7 35.6) and than in poorly differentiated tumours (grade III: 18.9 37.3). Similarly, significant differences in pS2 content were found between positive estrogen receptor (ER) tumours and ER-negative tumours (29.1 46.5 vs 11.3 15.9, respectively; p<0.0001), as well as between positive progesterone receptor (PR) tumours and PR-negative tumours (29.1 49.8 vs 15.3 21.5, respectively; p < 0.05). CONCLUSIONS: The results suggest that pS2 may be a useful prognostic marker in breast cancer, and may also be useful to identify patients who are likely to benefit from hormone therapy.

Análisis del contenido citosólico de la proteína ps2 en el cáncer de mama / Analysis of the cytosolic content of the ps2 protein in breast cancer

Objetivo: Analizar los niveles citosólicos de pS2 en carcinomas de mama y su correlación con las diferentes características clínicas de las pacientes y de sus tumores.Material y métodos: Se determinaron por método inmunorradiométrico los niveles citosólicos de pS2 en 168 tumores de pacientes con cáncer de mama. Resultados: Los valores de pS2 variaron de 0 a 251 ng/mg proteína (media ñ DE: 21,8 ñ 38,1; mediana: 7,9 ng/mg proteína). Esos niveles de la proteína fueron significativamente (p < 0,05) más elevados en las pacientes premenopáusicas (27,6 ñ 45,2) que en las pacientes postmenopáusicas (19,5 ñ 33,8). Los niveles intratumorales de pS2 también estuvieron significativamente (p < 0,05) correlacionados con el grado histológico de los tumores, siendo más elevados en los tumores bien diferenciados (grado I: 28,8 ñ 42,8) que en los tumores moderadamente diferenciados (grado II: 19,7 ñ 35,6) y que en los tumores pobremente diferenciados (grado III: 18,9 ñ 937,3). Similarmente, se encontraron diferencias significativas en el contenido de pS2 entre los tumores receptor de estrógeno (RE)-positivos y los tumores RE-negativos (29,1 ñ 46,5 vs 11,3 ñ 15,9, respectivamente; p < 0,0001), así como también entre los tumores receptor de progesterona (RP)-positivos y los tumores RP-negativos (29,1 ñ 49,8 vs 15,3 ñ 21,5, respectivamente; p < 0,05). Conclusión: Estos resultados sugieren que la pS2 puede ser un útil marcador pronóstico en el cáncer de mama, así como también para identificar pacientes que pueden beneficiarse de terapia hormonal (AU)

Clinical significance of epidermal growth factor receptor content in gastric cancer.

The objective of this work was to evaluate the epidermal growth factor receptor (EGFR) content in gastric cancer, its possible relationship with clinicopathological parameters of tumors and its prognostic significance. Membranous EGFR levels were examined by radioligand binding assays in 110 patients with gastric cancer. The mean follow-up period was 30.7 months. EGFR levels of tumors ranged widely, from 0.3 to 510 fmol/mg protein. EGFR levels were significantly higher (p<0.0005) in neoplastic tissue than in paired adjacent mucosa samples (median) (n= 84; 8.7 vs. 3.9 fmol/mg protein). Intratumoral EGFR levels were significantly correlated with tumor stage (p<0.05), and were higher in patients with stage III tumors (median) (7.6, 6.4, 12.3 and 7.5 fmol/mg protein for stages I, II, III and IV, respectively). In addition, the tumor/mucosa ratios of the EGFR content were significantly higher (p<0.05) in patients with stage III tumors (1, 1.8, 3.9, and 0.92, respectively). Although there was no significant relationship between EGFR levels of tumors and overall survival, the results suggest a role for EGFR in tumor progression of gastric cancer.

Estrogen and progesterone receptors in colorectal cancer and surrounding mucosa.

In this prospective study we have quantified by means of ELISA-methods the cytosolic content of estrogen (ER) and progesterone receptors (PgR) in tumoral tissue and paired normal mucosa from 163 patients with resectable colorectal cancer. Survival analysis was performed in a subgroup of 120 patients and the mean follow-up period was 24.9 months. The cutoff for ER and PgR levels was set at 1 fmol/mg protein. On the basis of this cutoff 20.9% of the cancers were ER positive and 25.8% were PgR positive; normal adjacent tissue presented ER in 18.4% and PgR in 24.5%. Our results did not show any significant correlation between ER and PgR levels in neoplastic tissues. Howewer, a correlation was found in normal mucosa samples (p=0.02). Statistical analysis showed that there was no correlation between tumor ER and PgR content and patient age or sex, tumor location, Dukes' stage, histological differentiation, DNA ploidy status and S-phase fraction. Furthermore, the results did not show any statistical differences in relapse-free and overall survival curves calculated for patients classified according to the hormone receptor content of their tumors. ER and PgR were detected at low levels in normal and neoplastic colorectal tissues without any significant relationship to either clinicopathological tumor characteristics or patient outcome. Their possible role in colorectal cancer remains to be elucidated.