Factores que inciden en la compra de alimentos en distintos ámbitos de comercialización y su relación con la implementación de educación alimentaria nutricional (EAN) / Factors influencing the purchase of foods in different marketing settings, and their relation to the implementation of food and nutrition education (FNE)

La Educación Alimentaria Nutricional (EAN) promueve la adquisición por parte de la población de conductas saludables permanentes relativas a la producción, selección, compra, preparación y utilización de alimentos, valiéndose de variados espacios sociales. Los canales minoristas de comercialización de alimentos urbanos ¹categorizados en dos grandes grupos: ferias/mercados y supermercados/hipermercados- constituyen espacios potenciales para la EAN, con diferencias importantes entre ellos. Los primeros ofrecerían canales de comunicación interpersonales más directos que los segundos. Ambos canales proponen un desafío en cuanto a estrategias y redes comunicacionales alternativas. Los dos escenarios están siendo estudiados para conocer y comprendermotivaciones, conductas, hábitos, orientaciones en las acciones, valores, conocimientos sobre hábitos de alimentación saludables y nutrición; canales de comunicación utilizados; información provista por consumidores y vendedores sobre conductas alimentarias y nutricionales; factores determinantes de la compra de alimentos para, a partir de esos insumos, proponer el desarrollo de posibles intervenciones de EAN. En el marco de un estudio cualitativo exploratorio y descriptivo, trabajando con datos de fuente primaria obtenidos mediante distintas técnicas cualitativas de investigación (observaciones, entrevistas) se plantea como objetivo general identificar y caracterizar distintos factores que influyen en el proceso de selección y compra de alimentos en canales minoristas de comercialización de Capital Federal con la finalidad de plantear acciones posibles de Educación Alimentaria. Se considera que existen diferencias significativas entre estos dos tipos de canales de comercialización y en los clientes que predominantemente concurren a unos y a otros comercios...(AU)

Factores que inciden en la compra de alimentos en distintos ámbitos de comercialización y su relación con la implementación de educación alimentaria nutricional (EAN) / Factors influencing the purchase of foods in different marketing settings, and their relation to the implementation of food and nutrition education (FNE)

La Educación Alimentaria Nutricional (EAN) promueve la adquisición por parte de la población de conductas saludables permanentes relativas a la producción, selección, compra, preparación y utilización de alimentos, valiéndose de variados espacios sociales. Los canales minoristas de comercialización de alimentos urbanos –categorizados en dos grandes grupos: ferias/mercados y supermercados/hipermercados- constituyen espacios potenciales para la EAN, con diferencias importantes entre ellos. Los primeros ofrecerían canales de comunicación interpersonales más directos que los segundos. Ambos canales proponen un desafío en cuanto a estrategias y redes comunicacionales alternativas. Los dos escenarios están siendo estudiados para conocer y comprendermotivaciones, conductas, hábitos, orientaciones en las acciones, valores, conocimientos sobre hábitos de alimentación saludables y nutrición; canales de comunicación utilizados; información provista por consumidores y vendedores sobre conductas alimentarias y nutricionales; factores determinantes de la compra de alimentos para, a partir de esos insumos, proponer el desarrollo de posibles intervenciones de EAN. En el marco de un estudio cualitativo exploratorio y descriptivo, trabajando con datos de fuente primaria obtenidos mediante distintas técnicas cualitativas de investigación (observaciones, entrevistas) se plantea como objetivo general identificar y caracterizar distintos factores que influyen en el proceso de selección y compra de alimentos en canales minoristas de comercialización de Capital Federal con la finalidad de plantear acciones posibles de Educación Alimentaria. Se considera que existen diferencias significativas entre estos dos tipos de canales de comercialización y en los clientes que predominantemente concurren a unos y a otros comercios...

Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies.

The Ku70/80 heterodimer is the regulatory subunit of the DNA-dependent protein kinase (DNA-PK) and its DNA-binding activity mediates DNA double-strand breaks repair. Although Ku80 was recently proposed as a caretaker gene involved in the control of genome integrity, no data are available on Ku70/80 DNA-binding activity in human tumors. Heterodimer DNA-binding activity and protein expression were assayed by electrophoretic-mobility-shift-assay (EMSA) and Western blot analysis, in nuclear and cytoplasmic extracts from eight breast, seven bladder primary tumors and three metastatic nodes from breast cancers. Corresponding normal tissues of the same patients were used as controls. Ten out of 15 tumors showed nuclear Ku-binding activity 3-10 times higher than in the normal tissues, irrespective of bladder or breast origin. Conversely, in 5/15 primary tumors and in all the metastatic nodes analysed, nuclear Ku-activity was 1.5-4.5-fold lower than in the corresponding normal tissues. Cytoplasmic heterodimer activity significantly differed between tumor and normal tissues, displaying a 2-10-fold increase in neoplastic tissues. Three different patterns combining both Ku expression and activity with tumor characteristics were identified. In low aggressive breast tumors p70/p80 proteins were expressed in tumor but not in normal tissues. The heterodimer binding-activity matched the protein levels. In non-invasive bladder carcinomas no significant differences in protein expression between tumor and the corresponding normal tissues were found, however heterodimer binding-activity was increased in tumor samples. In breast and bladder tumors, at the advanced stage and in node metastases, the binding activity was strongly reduced in tumor biopsies, however no differences were demonstrated between normal and tumor protein levels. Our results suggest a different modulation of Ku70/80 DNA-binding activity in human neoplastic tissues, possibly related to tumor progression. Findings provide further data on tissue-specific protein expression and post-translational regulation of heterodimer activity.

Codon 89 polymorphism in the human 5 alpha-reductase gene in primary breast cancer.

The enzyme human steroid 5-alpha reductase type II (SRD5A2) and androgen receptor (AR) are critical mediators of androgen action, suggesting a potential role in hormonally related cancers. The SRD5A2 gene harbours two frequent polymorphic sites, one in the coding region, at codon 89 of exon 1, where valine is substituted by leucine (V89L) and the other in the 3' untranslated region (3' UTR) where a variable number of dinucleotide TA repeat lengths exists. The V89L polymorphism is known to alter the activity of this enzyme. In the present study we examined 144 sporadic breast tumours from Italian patients for the V89L and TA polymorphisms by sequence and fragment analysis, respectively. Tumour extract prostate specific antigen (PSA) concentration as well as a number of well-established clinical and pathological parameters were evaluated. The results show that 53% of the tumours were homozygous for VV alleles, 37% were heterozygous for VL alleles and 10% were homozygous for LL alleles. TA(0) repeats were found in tumours with VV, LL and VL genotypes. TA(9) repeats were only found in VV homozygotes and were totally absent from either LL homozygotes or VL heterozygotes. PSA expression was significantly elevated in tumours with VV genotype. The presence of LL alleles in breast tumours is associated with earlier onset and shorter disease-free (RR = 2.65;P = 0.013) and overall survival (RR = 3.06;P = 0.014) rates. The VV genotype is associated with a more favourable prognosis. Our study suggests that the polymorphism in codon 89 of exon 1 of the human 5 alpha-reductase gene is related with TA repeat genotypes, PSA expression and breast cancer prognosis. More specifically, we found that the LL genotype is also associated with earlier onset and more aggressive forms of breast cancer. Long-term-outcome studies are needed to investigate the relevance of this polymorphism to breast cancer susceptibility.

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Sentinel lymph node and breast cancer staging: final results of the Turin Multicenter Study.

AIM OF THE STUDY: Validation of the sentinel node (SN) technique in breast cancer by means of lymphoscintigraphy. MATERIALS AND METHODS: From December 1996 to January 1999 102 T1-T2 breast carcinoma cases were recruited in Turin. 99mTc-human serum albumin colloids were injected subdermally the day before surgery (mean activity, 5.2 +/- 2.5 MBq). Scintigraphic imaging was performed after injection. After identification of the SN during surgery by a hand-held gamma probe, the SN was excised and sent for histologic examination. SN histology was compared with that of other axillary nodes. RESULTS: The SN detection rate was 86.3%; among 88 cases with an identified SN, 37 (42%) had axillary metastases; the SN was metastatic in 35 cases (sensitivity, 94.6%); in 51.3% of pN+ cases (19/37) the SN was the only metastatic site. In two of the 53 negative SNs, SN histology did not match with that of the remaining axilla (negative predictive value, 96.2%; staging accuracy, 97.7%). CONCLUSIONS: Our results agree with those reported in the literature; however, except in clinical trials and experienced structures axillary lymph node dissection should not be abandoned when mandatory for prognostic purposes, considering that at present SN biopsy alone is not completely accurate for axillary staging, especially in the absence of an adequate learning period.

Breast cancer prognostic significance of a single nucleotide polymorphism in the proximal androgen response element of the prostate specific antigen gene promoter.

Prostate Specific Antigen (PSA) expression by breast epithelial cells is associated with favorable breast cancer prognosis. In preliminary studies, we found that a nucleotide variation (G-->A) at position -158 in the androgen response element (ARE-1) of the PSA promoter was present in four out of 9 breast tumors examined and in a breast carcinoma cell line. We have now determined the nucleotide composition at position -158 of DNA extracted from 148 well-characterized breast tumors and compared tumor genotype with that of controls without cancer, with tumor PSA concentration and with clinicopathological variables, overall survival and disease free survival. The G-->A base change at position -158 is a polymorphism. Allelotypes were similarly distributed in breast cancer patients and controls. The Mann-Whitney U Test showed a significantly higher tumor PSA concentration in tumors that presented a homozygous G as opposed to homozygous A genotype. Genotype at position -158 was not associated with clinicopathological variables in contingency table analysis. Univariate Cox regression models showed a 28% reduction in risk for death in patients with homozygous G genotype compared to those with homozygous A genotype (P = 0.03). However, ARE-1 genotype did not significantly add to the prognostic power in the multivariate model of overall survival. In summary, the base change at position -158 is a polymorphism that may affect breast cancer prognosis, but further studies are required to confirm this possibility and to investigate the relevance of this polymorphism in terms of breast cancer susceptibility.

Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial. boccardo@hp380.ist.unige.it.

PURPOSE: To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients with early breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive either six cycles of a standard regimen of cyclophosphamide 100 mg/m(2) orally days 1 to 14, methotrexate 40 mg/m(2) intravenously (IV) days 1 and 8, and fluorouracil 600 mg/m(2) IV days 1 and 8 (CMF), with all drugs restarted on day 29, or 5 years of tamoxifen, 30 mg/d, plus ovarian suppression with surgical oophorectomy, ovarian irradiation, or monthly goserelin 3.6-mg injections. Disease-free survival was the main study end point. Overall survival and toxicity were additional end points. RESULTS: Between 1989 and 1997, 120 patients were assigned to CMF and 124 to tamoxifen and ovarian suppression (oophorectomy, n = 6; ovarian irradiation, n = 31; and goserelin injections, n = 87). At the time of analysis (median follow-up time, 76 months; range, 9 to 121 months), 82 patients had relapsed and 39 had died. No difference between groups had emerged with respect to either disease-free or overall survival. Treatments were comparable even in respect to age, tumor size, and nodal status, although a nonsignificant trend favored patients with poorly differentiated tumors treated with CMF. Leukopenia, nausea, vomiting, stomatitis, and alopecia were significantly more common in patients treated with CMF. There were few patients who developed benign gynecologic changes in either group, and numbers were comparable. CONCLUSION: The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to standard CMF.

TA repeat polymorphism of the 5alpha-reductase gene and breast cancer.

There is increasing evidence that androgens play a significant role in the development and progression of breast cancer. 5alpha-Reductase (SRD5A2) is an enzyme that is expressed in androgen-dependent tissues, and it catalyzes the reduction of testosterone to its more bioactive form, dihydrotestosterone, which then transactivates a number of genes. One of these genes encodes for prostate-specific antigen (PSA), a favorable prognostic factor in breast cancer. The 3' untranslated region of the SRD5A2 gene contains either no TA repeats [(TA)0] or 9 [(TA)9] or 18 [(TA)18] repeats. Variations in the length of these dinucleotide repeats have been reported to influence the enzymatic activity of SRD5A2. In this study, we determined the TA genotypes in DNA from 141 well-characterized breast tumors and in DNA from whole blood of 70 women without cancer. The presence of TA genotypes was then associated with tumor cytosolic PSA concentrations and with clinicopathological variables, including disease-free survival and overall survival. Three genotypes, (TA)0 homozygote, (TA)0/(TA)9 heterozygote, and (TA)9 homozygote, were identified. No (TA)18 alleles were detected in any of the two patient groups. A statistically significant association between high PSA concentrations and (TA)0/(TA)9 or (TA)9 genotypes was observed (P = 0.004). (TA)0/(TA)9 or (TA)9 genotypes were found less frequently in patients at stage III or IV disease. TA genotypes were not associated with other clinicopathological variables by contingency table analysis. Patients with (TA)0/(TA)9 or (TA)9 repeats, when compared to those with genotypes homozygous for the (TA)0 allele, showed a significant reduction in the risk for relapse (P = 0.043). Long-term studies are needed to investigate the relevance of this polymorphism to breast cancer susceptibility.

Shorter CAG repeat length in the androgen receptor gene is associated with more aggressive forms of breast cancer.

The androgen receptor (AR) is a transcription factor mediating the action of androgens. The AR gene is localized on chromosome X and it contains a series of CAG trinucleotide repeats. The length of the CAG repeats varies among individuals and this polymorphism is believed to be related to AR transcriptional activity. Studies have shown that fewer CAG repeats are associated with an increased risk as well as more aggressive forms of prostate cancer. Although AR is expressed in breast cancer and the impact of androgen and AR on breast cancer has been recognized, the role of the CAG repeats in breast cancer remains unknown. In this study, we measured the CAG repeats in breast cancer tissue using a PCR-based method. Of the 133 patients with primary breast cancer, 102 were heterozygous and 31 were homozygous. The mean CAG repeat number for homozygous women was 21; for heterozygous women the repeat number mean was 20 for the short allele and 24 for the long allele. The length of CAG repeats either in one allele or in both alleles was inversely correlated with the histological grade of breast cancer (r = -0.23 or -0.26, respectively, p < 0.05). An association between positive lymph nodes and fewer CAG repeats in both alleles was also suggested (p = 0.06). Furthermore, survival analysis indicated that the total number of CAG repeats in both alleles was associated with patient overall survival. With every CAG repeat increase, there was a 6% reduction in the risk of death (RR = 0.94, p = 0.03). The association remained significant after controlling for the homozygous and heterozygous status (RR = 0.92, p = 0.01). The association became no longer significant when clinical and pathological variables were adjusted in the analysis but this could be due to the reduction of sample size in the multivariate analysis. CAG heterozygosity and difference in number of CAG repeats between the two alleles were not associated with either disease features or patient survival. Our results suggest that longer CAG repeats may occur more frequently in less aggressive cancer and that the CAG repeats may play a role in breast cancer progression.

p53 gene mutation, tumor p53 protein overexpression, and serum p53 autoantibody generation in patients with breast cancer.

OBJECTIVES: Autoantibodies against the p53 tumor suppressor protein have been detected in the serum of a proportion of patients with various cancers. The generation of such antibodies has been proposed to be due to either tumor p53 protein accumulation or to the type of p53 gene mutation. These hypotheses are examined in the present study. DESIGN AND METHODS: Using immunofluorometric assays, we studied 195 patients with primary breast cancer for the presence of p53 antibodies in serum and p53 protein accumulation in the corresponding tumor. Seventeen patients (9%) were p53 antibody-positive and 77 (40%) overexpressed p53. Ten of the 17 p53 antibody-positive patients had tumor p53 accumulation and 7 were negative for p53. Statistical analysis revealed a weak association between the presence of p53 antibodies and p53 protein accumulation (p = 0.05). Direct DNA sequencing of exons 1-11 of the p53 gene was performed for 16 p53 antibody-positive and 16 p53 antibody-negative patients. RESULTS: Five of the seropositive and eight of the seronegative patients had a p53 gene mutation. Four of the five mutations in the p53 antibody-positive patients affected a Tyr residue, whereas none of the gene abnormalities in the seronegative patients had such an effect. CONCLUSIONS: We conclude that p53 antibodies tend to develop in patients with tumor p53 accumulation, but p53 accumulation is neither sufficient nor necessary for the generation of the immune response. Further, p53 antibody-positive patients do not have higher frequency of p53 gene mutations than p53 antibody-negative patients, but the former patient group is associated with a Tyr substitution in the protein product.

Serum total and free prostate-specific antigen for breast cancer diagnosis in women.

Prostate-specific antigen (PSA) is a serine protease expressed at high levels in prostate epithelium, and elevated PSA in serum is a well-established marker of prostate cancer. Recently, the relative proportions of free PSA and PSA complexed to the serine protease inhibitor alpha 1-antichymotrypsin have become important variables in distinguishing between prostate cancer and benign prostatic hyperplasia. Numerous studies have demonstrated the production of PSA in female tissues such as the breast, and low levels of PSA are present in female sera. The objective of this study was to measure and compare the relative proportions of free PSA and PSA complexed to the serine protease inhibitor alpha 1-antichymotrypsin in the serum of women with breast cancer or benign breast disease or women with no known malignancies. PSA was measured with an established immunoassay for total PSA and a novel immunoassay for free PSA, both of which had a detection limit of 0.001 microgram/liter (1 ng/liter). The percentage of breast cancer patients with free PSA as the predominant molecular form (> 50% of total PSA) in serum was five times higher than that of healthy women or women with benign breast disease, and PSA decreased in the serum of breast cancer patients after surgery. The diagnostic use of free PSA for breast cancer is limited at this point, due to the low diagnostic sensitivity (approximately 20%); however, free PSA as the predominant molecular form shows a high diagnostic specificity (approximately 96%) in comparison to women free of breast cancer or with benign breast disease. These results suggest that the clinical applicability of free PSA for breast cancer diagnosis and the biological mechanism behind its increase should be further investigated.

Serum levels of CA 125 and TPS during treatment of ovarian cancer.

Two hundred and sixty ovarian cancer patients (including all FIGO stages) were enrolled in a prospective multicentre study. In this interim study we analyzed 206 patients receiving combined chemotherapy for at least 3 courses for two-year overall survival (OS). CA 125 and TPS were applied for monitoring treatment and the relationship between marker levels, marker changes and clinical assessments was established. Preoperative CA 125 or TPS levels were not correlated with OS in FIGO stage I and II patients. After 3 chemotherapy courses the marker levels were not correlated with OS in stage I and II. Partial debulking in stage II patients was a bad prognostic factor. CA 125 or TPS levels (using a CA 125 discrimination level of 25 kU/l and a TPS discrimination level of 100 U/l) after 3 courses of chemotherapy were highly significantly correlated with OS in FIGO stages III and IV patients: CA 125 two-year OS 67% versus 26% (p < 0.0001) and TPS two-year OS 55% versus 22% (p < 0.0001). The prognostic value of CA 125 levels after 3 chemotherapy courses could be further increased by combining CA 125 and TPS levels. When both CA 125 and TPS levels were below their respective discrimination levels, the two-year overall survival was 75%. When both levels were above the discrimination level, the two-year overall survival was only 17%.

HRT, breast and endometrial cancers: strategies and intervention options.

The demand for hormone replacement therapy (HRT) by women who enter the menopause is rapidly increasing in all developed countries. The concern that HRT may enhance morbidity and mortality from malignant diseases still limits the widespread adoption of hormonal treatments. Overall, epidemiological data on cancer incidence and HRT are reassuring, although long-term or inappropriate therapies may slightly increase the risk of developing malignant diseases. Many commercial hormonal compounds are currently available and the safest HRT regimen with regard to cancer risk must be identified. It is equally important that the best strategies for breast and endometrial surveillance in women commencing HRT be outlined, bearing in mind that the diffusion of hormonal therapies may be halted by unnecessary medical interventions.

Prognostic significance of CA 125 and TPS levels after chemotherapy in ovarian cancer patients.

The analysis of survival data of patients with epithelial ovarian cancer proved that both CA 125 and TPS were good markers for clinical outcome prediction. Patients receiving chemotherapy were analyzed for 2-year overall survival (OS). Kaplan-Meier survival analysis showed highly significant differences in OS between patients with stage I+II (survival for 2 years 68%) and stage III+IV (survival for 2 years 33%; p = 0.0008). CA 125 levels above or below 35 kU/I and TPS levels above or below 80 U/l after 3 chemotherapy courses were not significantly correlated with OS in stage I+II patients (p = 0.06 respectively 0.07). However, in the subgroup of patients with stage III+IV the cut-off levels of CA 125 and TPS were excellent discriminators of OS: With CA 125 levels below the cut-off 52% of the patients survived, while with CA 125 levels above the cut-off only 13% survived (p < 0.0001). With TPS levels below the cut-off 49% of the patients survived, while with levels above the cut-off only 19% of the patients survived (p < 0.0001). In the subset of patients with CA 125 levels less than 35 kU/I after 3 chemotherapy courses (n = 50) analysis of their TPS levels allowed further discrimination of the prognostic significance. With TPS levels below the cut-off 63% of the patients survived, while 35% of the patients survived with TPS levels above the cut-off. The sum value of CA 125 and TPS cut-off values (115) as discriminator correlated even better with survival rate: With levels below this sum value 63% of the patients survived, while this was only 17% with sum values above the summed cut-off level (p = 0.0004). The extent to which the tumor was removed at operation also correlated with the 2 years survival rate. None of the patients with a staging laparotomy (n = 10) showed a 2-years survival. The difference in OS between patients with complete debulking and partial debulking was significant: OS 51% versus 23% (p = 0.027). Prognosis was not significantly correlated with histological type.

Immunoenzymatically determined pepsinogen C concentration in breast tumor cytosols: an independent favorable prognostic factor in node-positive patients.

The aim of this study was to determine the concentration and to evaluate the prognostic value of pepsinogen C (PepC) in breast cancer patients. PepC is an aspartic proteinase that is involved in the digestion of proteins in the stomach and is also synthesized by a subset of human breast tumors. PepC concentrations were measured with a highly sensitive immunofluorometric assay, which uses two monoclonal antibodies that are specific for PepC and has a detection limit of 0.1 ng/ml. Breast tumor cytosols from 151 patients (median follow-up, 67 months), stratified according to nodal status, were evaluated. An optimal cutoff value, equal to 1.75 ng/mg of extracted protein, was first defined by statistical analysis. PepC status was then compared with other established prognostic factors, in terms of disease-free survival (DFS) and overall survival (OS). High PepC concentrations were found in small (P = 0.003) and well-differentiated tumors (P = 0.042) as well as in stage I (P = 0.003) and node-negative patients (P = 0.040). Statistically significant associations of PepC concentration with patient age and estrogen receptor and progesterone receptor status were not observed. In univariate Cox regression analysis of the entire cohort of patients, negative PepC proved to be a significant predictor of reduced DFS (P = 0.0086) and OS (P = 0.025). Multivariate analysis in subgroups of patients defined by nodal status indicated that PepC status was a strong predictor of DFS (P = 0.0039) and the strongest factor for predicting OS (P = 0.0046) in node-positive but not in node-negative patients. Our results suggest that PepC may be used as an independent favorable prognostic factor in node-positive breast cancer patients because there were no significant associations between PepC and the other prognostic factors evaluated in this group of patients.

Prostate specific antigen molecular forms in breast cyst fluid and serum of women with fibrocystic breast disease.

We have analyzed matched serum and breast cyst fluid samples for total PSA from 148 patients with fibrocystic breast disease. We have also determined the molecular forms of PSA (free PSA and PSA bound to alpha1-antichymotrypsin) in 78 breast cyst fluid samples. We found that total PSA can be detected in all cyst fluids and in about 75% of female sera. The median total PSA concentration in breast cyst fluid (bcf) is about 30 times higher than the median in the corresponding sera. Breast cyst fluid and serum PSA are not correlated with each other. Total serum PSA is inversely associated with patient age but the inverse association between bcf PSA and age is weak. Lower total PSA in bcf was seen in women who breast feed, and higher bcf PSA is associated with multiple cysts. Type I cysts (with a high K+/ Na+ ratio) tend to have higher total PSA than Type II cysts. All but three of the fractionated cyst fluids (75/78; 96%) had free PSA as the predominant molecular form. The most consistent finding of our study was the positive association between the cyst fluid K+/Na+ ratio and the free to bound PSA ratio. This association was confirmed by Spearman correlation as well as by Wilcoxon and chi-square analysis. Secretory/apocrine cysts (Type I) tend to have more total PSA and proportionally more free PSA than transudative/flattened cysts (Type II).

Quantification of pepsinogen C and prostaglandin D synthase in breast cyst fluid and their potential utility for cyst type classification.

OBJECTIVE: To quantify pepsinogen C (PEPC) and prostaglandin D synthase (PGDS) in breast cyst fluid and examine if these two parameters can be used for breast cyst type classification. DESIGN AND METHODS: We quantified PEPC and PGDS in 92 and 50 breast cyst fluids, respectively, using previously established immunofluorometric procedures. We then examined if the levels of PEPC or PGDS correlate with the type of cyst or with other clinicopathological variables. RESULTS: Quantitative analysis of the breast cyst fluids indicated that PEPC is present in all cyst fluids at various concentrations ranging from 3 to 31,000 ng/mL. PGDS positivity was confined to 30% of the cyst fluids. PEPC and PGDS levels were correlated with the breast cyst fluid cation ratio and were associated with the type of the cyst. Increased PEPC levels in breast cyst fluids were significantly correlated with a > or = 1.5 K+/Na+ ratio and were associated with the secretory/apocrine type of cyst (Type I) (p = 0.011). Immunoreactive PGDS levels were highly correlated with a low cation ratio and were associated with the transudative/flattened type of breast cyst (Type II) (p = 0.0003). A weak association was observed between PEPC levels in breast cyst fluid and menopausal status (p = 0.093). No significant associations were observed for either PEPC or PGDS concentration in breast cyst fluid and number of cysts, recurrence of the disease, family history of breast cancer, number of children, abortion, and breast feeding. CONCLUSIONS: Quantification of PEPC and PGDS in breast cyst fluid may be useful in the subclassification of cyst type in patients with gross cystic disease.

Overexpression of the RON gene in human breast carcinoma.

Constitutive activation of the RON gene, known to code for the tyrosine-kinase receptor for Macrophage Stimulating Protein (also known as Scatter Factor 2), has been shown to induce invasive-metastatic phenotype in vitro. As yet, nothing is known about the expression of this novel member of the MET-oncogene family in spontaneously occurring human cancers. Here we report that Ron is expressed at abnormally high levels in about 50% primary breast carcinomas (35/74 patients). Among these, the expression is increased more than 20-fold in 12 cases and the overexpressed protein is constitutively phosphorylated on tyrosine residues. Notably, Ron is only barely detectable in epithelial cells of the mammary gland, and its expression remains unchanged in benign breast lesions (including adenomas and papillomas). Overexpression was observed in different histotypic variants of carcinomas; it is associated with the disease at any stage and correlates with the post-menopausal status. In breast carcinoma cells grown in vitro, activation of the Ron receptor resulted in proliferation, migration and invasion through reconstituted basement membranes. Altogether, these data suggest a role for the RON gene in progression of human breast carcinomas to the invasive-metastatic phenotype.