Clinical significance of cathepsin D concentration in tumor cytosol of primary breast cancer.

BACKGROUND: Cathepsin D is the proteolytic enzyme most frequently implicated as a prognostic factor in primary breast cancer. In the present study we evaluated by means of an immunoradiometric assay the tumor content of this protease in primary breast cancer, its relationship with tumor-related clinical and pathological parameters, and its prognostic significance in a large series of breast cancer patients. METHOD: The study comprised 1033 women with histologically established invasive breast cancer. Cathepsin D was measured in cytosol samples by means of an immunoradiometric assay to determine the total amount of cathepsin D (52 kDa, 48 kDa and 34 kDa). Evaluation of relapse-free survival and cause-specific survival was performed in the group of 1003 patients without evidence of metastasis at the time of initial diagnosis. The median follow-up of the patients who were free of recurrence was 54 months. RESULTS: Cathepsin D levels showed a wide range among the studied tumors (n = 1033; median (range) 41 (0.9-2504) pmol/mg protein). Statistical analysis showed that the median cathepsin D levels were considerably higher in large tumors (T2-4) than in smaller ones (T1) (p = 0.017), as well as in node-positive than in node-negative tumors (p = 0.004). Cathepsin D levels were also higher in ductal tumors than in the other histological types (p = 0.001), as well as in moderately or poorly differentiated tumors (p < 0.001). Likewise, the median value of the protease was significantly higher in ER or PgR-positive tumors than in hormone receptor-negative ones (p = 0.011 and p = 0.004, respectively), as well as in aneuploid tumors than in diploid tumors (p = 0.029). Multivariate analysis demonstrated that elevated cathepsin D levels (> 59 pmol/mg protein) were notably associated with a shorter cause-specific survival in the whole group of patients with breast cancer, as well as in the subgroup of node-positive patients (p < 0.05). CONCLUSIONS: This study suggests that elevated intratumoral cathepsin D levels may identify a subset of node-positive breast cancer patients showing a high probability of earlier death.

Clinical significance of cathepsin D concentration in tumor cytosol of primary breast cancer.

BACKGROUND: Cathepsin D is the proteolytic enzyme most frequently implicated as a prognostic factor in primary breast cancer. In the present study we evaluated by means of an immunoradiometric assay the tumor content of this protease in primary breast cancer, its relationship with tumor-related clinical and pathological parameters, and its prognostic significance in a large series of breast cancer patients. METHOD: The study comprised 1033 women with histologically established invasive breast cancer. Cathepsin D was measured in cytosol samples by means of an immunoradiometric assay to determine the total amount of cathepsin D (52 kDa, 48 kDa and 34 kDa). Evaluation of relapse-free survival and cause-specific survival was performed in the group of 1003 patients without evidence of metastasis at the time of initial diagnosis. The median follow-up of the patients who were free of recurrence was 54 months. RESULTS: Cathepsin D levels showed a wide range among the studied tumors (n=1033; median (range) 41 (0.9-2504) pmol/mg protein). Statistical analysis showed that the median cathepsin D levels were considerably higher in large tumors (T2-4) than in smaller ones (T1) (p=0.017), as well as in node-positive than in node-negative tumors (p=0.004). Cathepsin D levels were also higher in ductal tumors than in the other histological types (p=0.001), as well as in moderately or poorly differentiated tumors (p<0.001). Likewise, the median value of the protease was significantly higher in ER or PgR-positive tumors than in hormone receptor-negative ones (p=0.011 and p=0.004, respectively), as well as in aneuploid tumors than in diploid tumors (p=0.029). Multivariate analysis demonstrated that elevated cathepsin D levels (>59 pmol/mg protein) were notably associated with a shorter cause-specific survival in the whole group of patients with breast cancer, as well as in the subgroup of node-positive patients (p<0.05). CONCLUSIONS: This study suggests that elevated intratumoral cathepsin D levels may identify a subset of node-positive breast cancer patients showing a high probability of earlier death. (Int J Biol Markers 2005; 20: 103-11).

Collagenase-3 (MMP-13) expression in cutaneous malignant melanoma.

BACKGROUND: Matrix metalloproteases (MMPs), enzymes with the ability to degrade the extracellular matrix, play an important role in tissue invasion by cutaneous malignant melanoma (CMM). One specific MMP, collagenase-3 (MMP-13), is thought to have a key function in the activation of MMP. AIMS: To evaluate the expression of MMP-13 in CMM and assess its possible relationship to clinical and pathological parameters. METHODS: MMP-13 expression was analyzed in 51 paraffin-embedded tumor samples from patients with invasive CMM, ten samples from in situ melanomas, and in eight samples from benign lesions (three dermal melanocytic nevi, three compound melanocytic nevi and two atypical melanocytic nevi) using immunohistochemical techniques. The median follow-up period in patients with invasive CMM was 50 months. RESULTS: Benign lesions were consistently negative for MMP-13, whereas three of the ten in situ melanomas (30%) and 23 of the 51 invasive CMMs (45%) showed positive immunostaining for MMP-13. The percentage of MMP-13-positive tumors correlated significantly and positively with the mitotic index (p=0.002) in invasive CMM. However, our results did not show any significant association between tumoral MMP-13 expression and relapse-free survival in patients with invasive CMM. CONCLUSIONS: MMP-13 appears to be a factor associated with tumor aggressiveness in CMM. It seems to eliminate an important barrier not only against tumoral invasion but also against proliferation.

Significance of cytosolic hyaluronan levels in gastric cancer.

BACKGROUND: Hyaluronan a high-molecular weight glycosaminoglycan, is considered to be involved in the growth and progression of malignant tumours. The objective of this work was to evaluate the cytosolic hyaluronan content in gastric cancer cells, its possible relationship with clinicopathological tumour parameters and its potential prognostic significance. METHODS: Cytosolic hyaluronan levels were examined utilizing immunoenzymatic techniques in 129 patients with gastric cancer. The mean follow-up period for these patients was 28 months. RESULTS: Cytosolic hyaluronan levels ranged widely in tumours as well as in adjacent mucosal samples (median (range) 2822 (50-24,523) versus 3650 (507-20,782) ng/mg protein). Statistical analysis showed that tumour hyaluronan levels correlated significantly with patient's sex and the presence of lymphatic invasion. In addition, high tumour hyaluronan levels were significantly associated with shorter overall survival period (p<0.05). CONCLUSIONS: Our results suggest that high tumoral cytosolic hyaluronan levels are associated with lesions of unfavorable outcome in gastric cancer patients. Thus, hyaluronan may provide additional prognostic information to that given by other biochemical markers currently used in gastric cancer.

Cytosolic levels of an estrogen-induced breast cancer-associated peptide (TFF1/pS2) in colorectal cancer: clinical significance and relationship with steroid receptors.

BACKGROUND: The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA in MCF-7 breast cancer cells and is also expressed by colorectal carcinomas. The objective of this work was to evaluate the cytosolic TFF1 content in colorectal carcinomas, its possible relationship with estrogen and progesterone receptors as well as with clinicopathological tumor parameters, and its potential prognostic significance. METHODS: Cytosolic TFF1 levels were examined by immunoradiometric assay in 178 patients with resectable colorectal cancer. The mean follow-up period was 32 months. RESULTS: There was a wide variability of cytosolic TFF1 levels in tumor-surrounding mucosa samples (0.09-42.5 ng/mg protein) as well as in tumors (0.01-270 ng/mg protein). Comparison of paired mucosa and carcinoma samples showed significantly higher TFF1 levels in tumors (mean: 17.1 ng/mg protein) than in mucosa samples (10 ng/mg protein) (p = 0.027). TFF1 levels were significantly higher in mucosa samples surrounding distal colon and rectal tumors (p = 0.0001) and in tumor samples obtained from older patients (p = 0.007). However, there were no significant differences in tumor TFF1 levels with respect to clinicopathological parameters such as the patient's sex, tumor location, stage, histological grade, ploidy, S-phase, or tumor estrogen and progesterone receptors. In addition, there was no significant relationship between tumor TFF1 levels and disease outcome. CONCLUSIONS: TFF1 may play an as yet undetermined role in the tumorigenesis of colorectal carcinomas. However, cytosolic levels of TFF1 do not seem to have any prognostic significance in colorectal carcinomas.

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.

Importancia de la edad como factor pronóstico determinante de la variabilidad de las características clínico-patológicas de las pacientes con cáncer de mama / Importance of the age as factor determining prognosis of the variability of the clinical-pathological characteristics of patients with breast cancer

Objetivo: analizar la importancia de la edad como factor pronóstico en el cáncer de mama, lo cual podría tener importantes implicaciones en el tratamiento y manejo clínico de las pacientes. Material y métodos: estudio retrospectivo de 769 pacientes intervenidas quirúrgicamente por cáncer de mama (1983-1999). El tiempo medio de seguimiento fue de 34,4 meses. Se realizaron estudios bioquímicos para la determinación de receptores de estrógenos y progesterona, contenido de ADN y fase S. Resultados: la edad media de las 769 pacientes fue de 59 años, y la década de mayor presentación del cáncer de mama fue la de los 50 años (26,5 per cent). Encontramos una asociación estadísticamente significativa entre la edad de las pacientes y el tamaño tumoral (p<0,0001), grado histológico (p<0,018), contenido de receptores de estrógenos (p<0,014) y fase S (p<0,019). Las pacientes de menor edad tuvieron un mayor número de casos de tumores de menor ta maño, histológicamente menos diferenciados y con receptores estrogénicos negativos. El análisis univariante demostró que el mayor tamaño tumoral, el estadio nodal positivo y el grado histológico indiferenciado de los tumores estuvieron significativa y positivamente asociados con un menor tiempo libre de enfermedad y supervivencia total de las pacientes. Sin embargo, no existieron diferencias significativas en el pronóstico entre los diferentes grupos de pacientes clasificadas en función de sus distintas edades. Conclusiones: el presente estudio demuestra diferencias en las características clínicas, morfológicas y biológicas de los carcinomas mamarios en función de la edad de las pacientes. Sin embargo , nuestros resultados no demostraron diferencias significativas en el pronóstico de las pacientes en función de su edad. Ello podría tener importantes implicaciones de cara al tratamiento y manejo clínico de las pacientes, principalmente de aquellas de más avanzada edad (AU)

[Traumatic perforation of the small intestine in childhood]. / Perforación traumática del intestino delgado en la infancia.

INTRODUCTION: Traumatic perforation of the small bowel occurs in approximately 1 percent of children with either blunt or penetrating trauma to the abdomen. Difficulty in recognition of initial subtle signs of hollow viscus injury can lead to delay in both diagnosis and operative intervention. MATERIAL AND METHOD: Medical records for patients discharged with traumatic small bowel perforation from the General Surgery Department between 1991 and 1999 were reviewed. RESULTS: Bowel injuries were noted in 41 children. Blunt trauma (battered child syndrome, bike injuries, etc.), was responsible for 37 cases and penetrating wounds in three (firearm wounds and bike pedal accidents). There were 32 boys and a mean age of 6.8 years. The site of perforation was duodenal in four cases, jejunum in 21, and ileum in sixteen. Associated injuries occurred in 11 patients, including stomach, pancreas, liver, spleen, bladder, and ureter. Twenty-nine had simple closure, while seven were resected. Four children died. CONCLUSIONS: These injuries require prompt surgical intervention and are in general curable with excellent prognosis if one is alert to the possibility of their occurrence, if one is familiar with the approaches to prompt and accurate diagnosis, and if associated injuries are not serious.

[Diaphragmatic paralysis due to a lesion of the phrenic nerve secondary to venesection at the neck for parenteral feeding]. / Parálisis diafragmática por lesión del nervio frénico secundaria a venodisección en cuello para alimentación parenteral.

It is presented the clinical record of a female newborn of 39 weeks of gestational age, with birth weight of 4600 g, with diaphragmatic palsy eight days after birth. Were realized diaphragmatic plicature and the clinical course was without any complication. Were reviewed the causes of diaphragmatic palsy and was described the relationship, with vein cannulation for parenteral nutrition.