Residuo posmiccional y síntomas de disfunción de vaciado en mujeres con prolapso de órganos pélvicos antes y después de la cirugía vaginal. Estudio de cohortes multicéntrico / Post-void residual and voiding dysfunction symptoms in women with pelvic organ prolapse before and after vaginal surgery. A multicenter cohort study

OBJETIVOS: El presente trabajo evalúa el impacto de la cirugía vaginal del prolapso de órganos pélvicos (POP) en los síntomas de disfunción de vaciado (DV) y en el residuo posmiccional (RPM) un año después de la intervención. MATERIAL Y MÉTODOS: Estudio epidemiológico, longitudinal y prospectivo. Un total de 39 unidades de ginecología incluyeron mujeres con POP sintomático de grado 2 o superior según la clasificación Pelvic Organ Prolapse Quantification (POP-Q) que iban a ser sometidas a cirugía del prolapso por vía vaginal (estudio CIRPOP-IUE). Se recogieron variables sociodemográficas y clínicas antes y después de la intervención. En ambas visitas, las pacientes cumplimentaron los cuestionarios Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ) y Pelvic Floor Distress Inventory (PFDI-20). El RPM se midió por sondaje vesical inmediatamente después de una micción espontánea. RESULTADOS: El 50% de las mujeres refirieron síntomas de DV antes de la intervención. El RPM se midió en 277 mujeres de las cuales en 116 (41,87%) fue > 50 ml y en 42/277 (15,2%) fue > 100 ml. Un año tras la intervención, se observó una reducción objetiva y subjetiva de los síntomas de DV. El RPM medio se redujo de forma estadísticamente significativa, pasando de una media (DE) de 66,4 (68,9) ml a 48,3 (51,3) ml. También disminuyó el número de pacientes que reportaron dificultad de vaciado y sensación de vaciado incompleto en los cuestionarios EPIQ y PFDI-20. CONCLUSIONES: En general, se observó una mejora de la función miccional tanto a través de la disminución de los síntomas específicos de DV como de la reducción del volumen medio del RPM

OBJECTIVES: The present study evaluates the impact of vaginal surgery for pelvic organ prolapse (POP) on voiding dysfunction (VD) symptoms and post-void residual (PVR) one year after the intervention. MATERIAL AND METHODS: Epidemiological, longitudinal, prospective study. Thirty-nine gynecology units included women with symptomatic POP grade 2 or higher according to the Pelvic Organ Prolapse Quantification (POP-Q) system, who would undergo surgery for vaginal prolapse (CIRPOP-IUE study). Sociodemographic and clinical variables were collected before and after the intervention. At both visits, patients completed the 'Epidemiology of Prolapse and Incontinence Questionnaire' (EPIQ) and 'Pelvic Floor Distress Inventory' (PFDI-20) questionnaire. PVR volume was measured by bladder catheterization immediately after spontaneous urination. RESULTS: VD symptoms were present in 50% cases before the intervention. PVR was measured in 277 women of which 116 (41.87%) were > 50 ml and 42/277 (15.2%) were > 100 ml. Objective and subjective reduction in VD symptoms was observed one year after the intervention. Mean PVR volume was reduced with statistical significance, from a mean (SD) of 66.4 (68.9) ml to 48.3 (51.3) ml. The number of patients who reported difficulty in emptying and sensation of incomplete emptying on the EPIQ and PFDI-20 questionnaires also decreased. CONCLUSIONS: In general, improved voiding functions were observed in the CIRPOP-IUE study through a decrease in specific VD symptoms and a reduction in mean PVR volume

Post-void residual and voiding dysfunction symptoms in women with pelvic organ prolapse before and after vaginal surgery. A multicenter cohort study. / Residuo posmiccional y síntomas de disfunción de vaciado en mujeres con prolapso de órganos pélvicos antes y después de la cirugía vaginal. Estudio de cohortes multicéntrico.

OBJECTIVES: The present study evaluates the impact of vaginal surgery for pelvic organ prolapse (POP) on voiding dysfunction (VD) symptoms and post-void residual (PVR) one year after the intervention. MATERIAL AND METHODS: Epidemiological, longitudinal, prospective study. Thirty-nine gynecology units included women with symptomatic POP grade 2 or higher according to the Pelvic Organ Prolapse Quantification (POP-Q) system, who would undergo surgery for vaginal prolapse (CIRPOP-IUE study). Sociodemographic and clinical variables were collected before and after the intervention. At both visits, patients completed the 'Epidemiology of Prolapse and Incontinence Questionnaire' (EPIQ) and 'Pelvic Floor Distress Inventory' (PFDI-20) questionnaire. PVR volume was measured by bladder catheterization immediately after spontaneous urination. RESULTS: VD symptoms were present in 50% cases before the intervention. PVR was measured in 277 women of which 116 (41.87%) were >50ml and 42/277 (15.2%) were >100ml. Objective and subjective reduction in VD symptoms was observed one year after the intervention. Mean PVR volume was reduced with statistical significance, from a mean (SD) of 66.4 (68.9)ml to 48.3 (51.3)ml. The number of patients who reported difficulty in emptying and sensation of incomplete emptying on the EPIQ and PFDI-20 questionnaires also decreased. CONCLUSIONS: In general, improved voiding functions were observed in the CIRPOP-IUE study through a decrease in specific VD symptoms and a reduction in mean PVR volume.

Evaluating the results of stress urinary incontinence surgery with objective and subjective outcome measures.

OBJECTIVE: To assess the outcomes of stress urinary incontinence (SUI) surgery using objective and subjective measures in women with pure SUI and mixed urinary incontinence (MUI). The degree of correlation between the different outcome measures was also evaluated for both groups. STUDY DESIGN: A multicentre prospective cohort study of women who underwent surgery for SUI. A standardized cough stress test was used as the objective outcome measure, and specific items of the Epidemiology of Prolapse and Incontinence Questionnaire were used as the subjective outcome measure. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Patient Global Impression of Improvement (PGI-I) questionnaires were used for global assessment. Kappa test was used to measure the degree of correlation between the outcome measures. RESULTS: The participants were categorized into two groups before surgery: pure SUI (n=116) and MUI (n=161). Six months after surgery, the cure rate of the SUI component was high in both groups according to the objective and subjective outcome measures. Global assessment showed lower cure rates. The degree of agreement between objective and subjective outcome measures was moderate (kappa 0.541, p<0.001) for women with pure SUI, and fair (kappa 0.377, p<0.001) for women with MUI. Correlation between the change in ICIQ-UI SF score (pre to post surgery) and the degree of satisfaction (PGI-I) was significant (p<0.01) for both the pure SUI group (0.43) and the MUI group (0.48). CONCLUSIONS: Both objective and subjective cure rates are high for women with pure SUI and MUI following SUI surgery in Spain. The degree of agreement between different outcome measures varies.

Influence of mode of delivery on pelvic organ support 6 months postpartum.

AIMS: The aims of this study were to describe pelvic organ support 6 months postpartum among women who delivered by cesarean section, spontaneous and instrumental vaginal delivery, and to evaluate the differences between the groups. METHODS: This was a cross-sectional study of 382 primigravid women who gave birth at Donostia Hospital during 2007. Pelvic organ support was explored 6 months postpartum using the pelvic organ prolapse quantification (POPQ) system. Joint hypermobility, height and weight were also assessed. RESULTS: POPQ stage ≥II was present in 7.7, 18.1 and 29.0% of women who delivered by cesarean section, spontaneous and instrumental vaginal delivery, respectively. Spontaneous vaginal delivery increased the risk by more than three times (OR 3.19; 95% CI 1.07-9.49) while instrumental vaginal delivery increased it more than fivefold (OR 5.52; 95% CI 1.79-17.30) in comparison with cesarean section. Instrument-assisted delivery did not increase the risk of prolapse in women who delivered vaginally. CONCLUSIONS: Cesarean section is associated with a lower prevalence of pelvic organ prolapse after delivery. Instrument- assisted delivery is not associated with an increased risk of postpartum prolapse among women who delivered vaginally.

Incidence of overactive bladder after vaginal hysterectomy and associated repairs for pelvic organ prolapse.

OBJECTIVE: The aim of this study was to determine the incidence of overactive bladder (OAB) after vaginal hysterectomy for pelvic organ prolapse (POP) and analyze the associated risk factors. STUDY DESIGN: This was a retrospective cohort study of 217 patients who underwent primary POP vaginal surgery between the years 2000 and 2004 in Donostia Hospital and who did not report OAB before surgery. A personal interview was undertaken after surgery for the diagnosis of OAB, taking into account the ICS 2002 definition. Descriptive statistical analyses and multivariate logistic regression were performed to determine the factors associated with the development of OAB after POP surgery. RESULTS: De novo OAB was diagnosed in 43 (19.8%) patients. The median time at onset of OAB symptoms after surgery was 3 months. Urge urinary incontinence was present in 28 patients (12.9%). Those women operated on also for stress urinary incontinence were at an increased risk for de novo OAB. CONCLUSION: Nearly 20% of women operated on for POP develop OAB soon after surgery. Those operated on for POP and stress urinary incontinence are more at risk.

Risk factors for the recurrence of pelvic organ prolapse after vaginal surgery: a review at 5 years after surgery.

The objective of this study was to determine the factors associated with the anatomic and functional recurrence of prolapse. An examination was performed in 134 of the 228 patients who underwent primary vaginal surgery for prolapse of the pelvic organs (POP) between 2000 and 2001. Anatomical recurrence of the prolapse was established by pelvic examination using the pelvic organ prolapse quantification (POPQ) staging system. Functional results were obtained by interview with the patients. Descriptive statistical analyses and multivariate logistic regression were performed to determine the factors associated with recurrence. Five years after surgery, 42 women (31.3%) presented anatomical recurrence of the prolapse (grade > or = II), and only 10 of the 134 (7.4%) had prolapse-related symptoms. Those with high body weight (>65 kg) and younger women (<60 years) were associated with an increase in the risk for both anatomical and functional recurrence. Advanced preoperative prolapse (grade III-IV) of any compartment was associated with anatomical failure but not with symptomatic recurrence. There was a poor correlation between anatomical and symptomatic recurrence. Younger women and those with a higher body weight are more likely to experience recurrent prolapse after vaginal repair.

Expression of collagenase-3 in the rat ovary during the ovulatory process.

We have examined the expression of the murine counterpart of human collagenase-3, a matrix metalloproteinase produced by breast carcinomas, in the course of processes which involve extensive tissue remodeling. By using Northern blot analysis, we have found that collagenase-3 is expressed in the rat ovary, but not in the remaining analyzed tissues including brain, kidney, liver, lung, mammary gland, uterus, bladder, heart, intestine, prostate, spleen, testis and thymus. Collagenase-3 mRNA was detected at high levels in rat ovaries at proestrus and estrus, was at a minimum at metestrus and started to increase during diestrus through to proestrus. In addition, collagenase-3 was also detected on day 21 of pregnancy, which is approximately one day before parturition. However, no significative expression was detected in RNA from ovaries taken immediately after parturition, or on days 1, 5 or 30 postpartum. Northern blot analysis also revealed that collagenase-3 was not expressed at significant levels, compared with ovarian expression, in the uterus or in the mammary gland during pregnancy or after parturition. When follicular granulosa cells were separated from residual ovarian tissue and their RNA was analyzed by Northern blot, it was seen that collagenase-3 was not expressed by the granulosa cells but was present in the residual tissue containing interstitial and thecal tissues, growing follicles and corpora lutea. Immunohistochemical studies also confirmed, at the protein level, the localization of collagenase-3 in rat ovary. Gonadotropic stimulation of ovulation in immature rats by priming with pregnant mare's serum gonadotropin and stimulation with human chorionic gonadotropin failed to induce the expression of collagenase-3, suggesting that additional factors which are not present in the immature stimulated rats are needed for completely effective induction of the expression of this matrix metalloproteinase. On the basis of these results, together with the comparative analysis of expression of different matrix metalloproteinases in the rat ovary, we propose that collagenase-3 is a major ovarian metalloproteinase potentially involved in ovarian function during the reproductive cycle.

Pepsinogen C is a new prognostic marker in primary breast cancer.

PURPOSE: Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas. PATIENTS AND METHODS: Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months. RESULTS: A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated (grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively). CONCLUSION: Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution.

Relationship between serum prolactin levels and protein composition of breast secretions in nonlactating women.

The potential relationship between serum PRL levels and protein composition of breast secretions was evaluated in 54 premenopausal nonlactating women during the luteal phase of their menstrual cycle. Women were classified into four groups according to the presence or absence of breast pathology and to the protein pattern of their breast secretions. Type I mammary fluids contain Zn-alpha 2-glycoprotein, apolipoprotein D, and gross cystic disease fluid protein-15, whereas Type II fluids are characterized by the presence of some milk proteins such as lactoferrin, lysozyme, and alpha-lactalbumin. Basal serum levels of PRL, as well as of progesterone, LH, FSH, TSH, T3, and T4 were within normal range, and no significant differences were found between the different groups of women under study. However, after a TRH stimulation test, the maximum PRL response was significantly higher (P < 0.02) in normal women with Type II secretions than in those with Type I (64 +/- 6.8 micrograms/L vs. 43.7 +/- 3.9 micrograms/L). Similarly, when PRL concentrations in patients with benign breast disease were considered, those with breast fluids containing milk proteins had a rise in PRL secretion after TRH stimulation significantly higher (P < 0.05) than those with fluids lacking these proteins (77.1 +/- 6.2 vs. 58.8 +/- 5.1 micrograms/L). These results indicate that the occurrence of milk proteins in breast secretions from nonlactating women is associated with an increase in serum PRL concentrations after TRH stimulation, and opens the possibility of using breast fluid protein analysis as a simple and noninvasive procedure for studies on the putative role of PRL in the development of benign and malignant breast diseases.

Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas.

A cDNA coding for a new human matrix metalloproteinase (MMP) has been cloned from a cDNA library derived from a breast tumor. The isolated cDNA contains an open reading frame coding for a polypeptide of 471 amino acids. The predicted protein sequence displays extensive similarity to the previously known MMPs and presents all the structural features characteristic of the members of this protein family, including the well conserved PRCGXPD motif, involved in the latency of the enzyme and the zinc-binding domain (HEXGHXXXXXHS). In addition, this novel human MMP contains in its amino acid sequence several residues specific to the collagenase subfamily (Tyr-214, Asp-235, and Gly-237) and lacks the 9-residue insertion present in the stromelysins. According to these structural characteristics, the MMP described herein has been tentatively called collagenase-3, since it represents the third member of this subfamily, composed at present of fibroblast and neutrophil collagenases. The collagenase-3 cDNA was expressed in a vaccinia virus system, and the recombinant protein was able to degrade fibrillar collagens, providing support to the hypothesis that the isolated cDNA codes for an authentic collagenase. Northern blot analysis of RNA from normal and pathological tissues demonstrated the existence in breast tumors of three different mRNA species, which seem to be the result of the utilization of different polyadenylation sites present in the 3'-noncoding region of the gene. By contrast, no collagenase-3 mRNA was detected either by Northern blot or RNA polymerase chain reaction analysis with RNA from other human tissues, including normal breast, mammary fibroadenomas, liver, placenta, ovary, uterus, prostate, and parotid gland. On the basis of the increased expression of collagenase-3 in breast carcinomas and the absence of detectable expression in normal tissues, a possible role for this metalloproteinase in the tumoral process is proposed.

Expression and prognostic significance of apolipoprotein D in breast cancer.

Apolipoprotein D (apo D) is a glycoprotein involved in the human plasma lipid transport system and present at large amounts in cyst fluid from women with gross cystic disease of the breast. Apo D expression in breast carcinomas was examined by immunoperoxidase staining of a series of 163 tumors. A total of 60 (36.8%) tumors were negative for apo D immunostaining, 28 (17.2%) carcinomas were weakly positive, 33 (20.2%) were moderately stained, whereas the remaining 42 (25.8%) tumors were strongly stained with the specific antibodies. No significant correlation was found between apo D content and tumor size, lymph node involvement, or biochemical parameters such as estrogen receptors, cathepsin D, or pS2 protein. However, the finding of a significant association between apo D and menopausal status of patients or differentiation grade of tumors, with apo D values being lower in tumors from premenopausal women or in poorly differentiated carcinomas, suggested a potential value of this glycoprotein as a prognostic factor in breast cancer. Preliminary analysis of relapse-free survival and overall survival in a subgroup of 152 women with a mean follow-up of 42 months confirmed that low apo D values were significantly associated to a shorter relapse-free survival and poorer survival. According to these data, we propose that apo D in combination with other well-established prognostic factors may contribute to more accurately identify subgroups of breast cancer patients with low or high risk for relapse and death.

Glucocorticoids and androgens up-regulate the Zn-alpha 2-glycoprotein messenger RNA in human breast cancer cells.

We have studied the hormonal regulation of the gene encoding Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a human protein with a high degree of amino acid sequence similarity to class I histocompatibility antigens that is produced by a specific subset of breast carcinomas. Northern blot analysis revealed that dexamethasone and 5 alpha-dihydrotestosterone strongly induced the accumulation of Zn-alpha 2-gp mRNA in T-47D human breast cancer cells. Furthermore, the effect of these two hormones was shown to be additive, since the combination of both hormones produced a stimulation of Zn-alpha 2-gp mRNA of at least 3-fold over that produced by either hormone alone. By contrast, the addition of 5 beta-dihydrotestosterone, 17 beta-estradiol, or progesterone failed to induce the expression of Zn-alpha 2-gp. The stimulatory effect of glucocorticoids and androgens on Zn-alpha 2-gp expression was produced in a time and dose dependent manner, without significantly affecting the cell proliferation rate. A time-course study demonstrated that the induction of Zn-alpha 2-gp mRNA by androgens and glucocorticoids reached a level of 4 or 3.2-fold over the untreated control after seven days of incubation in the presence of a 10(-7) M concentration of 5 alpha-dihydrotestosterone or dexamethasone, respectively. A dose-response study showed that as little as 10(-11) M of 5 alpha-dihydrotestosterone or dexamethasone produced an accumulation of Zn-alpha 2-gp mRNA of 2.4 or 2.1-fold over the control, respectively. On the basis of these results, we propose that Zn-alpha2-gp may be useful as a biochemical marker of breast carcinomas with a specific pattern of hormone responsiveness in whose development glucocorticoids and/or androgens may play a significant role.

Expression of pepsinogen C in human breast tumours and correlation with clinicopathologic parameters.

We have examined by immunohistochemistry the ability of breast carcinomas to produce pepsinogen C, an aspartyl proteinase usually involved in the digestion of proteins in the stomach. A total of 113 out of 245 breast tumours (46%) were positive for pepsinogen C immunostaining. There was a significant association between pepsinogen C and oestrogen receptors with proteinase levels higher (HSCORE) in oestrogen receptor positive tumours than in oestrogen receptor negative. There was also a significant association between pepsinogen C and histological grade, pepsinogen C levels being higher in well and moderately differentiated breast carcinomas than in poorly differentiated tumours. On the basis of these results, we suggest that pepsinogen C may be useful as a marker of good prognosis in breast cancer.

Cathepsin D in breast secretions from women with breast cancer.

A proteinase accumulated in breast secretions from women with breast cancer has been characterised. Inhibition of the proteolytic activity of breast secretions by pepstatin A showed that the main enzyme involved was an aspartyl proteinase. Determination of its cleavage specificity by SDS-PAGE and amino acid sequence analysis revealed that it was identical to that of cathepsin D, an aspartyl proteinase suggested to be involved in breast cancer development. The identity between both proteins was further confirmed by immunological analysis with monoclonal antibodies against cathepsin D. Quantification of cathepsin D in nipple fluids from 41 women with benign or malignant breast diseases and from 19 control women without breast pathology revealed the presence of variable amounts of this proteinase. The average concentration of cathepsin D in breast secretions from cancer-bearing breasts was 7.2 +/- 2.2 fmol micrograms of protein, which was significantly higher than those of nipple fluids from control women (2.9 +/- 0.6 fmol micrograms-1) (P = 0.04) or from patients with benign breast diseases (2.1 +/- 0.3 fmol micrograms-1) (P = 0.004). Though the number of cancer patients studied was small (n = 21), no correlations were found with cytosolic concentrations of cathepsin D or oestrogen receptors, neither with other parameters such as tumour size, histological grade, axillary node involvement or menopausal status.

Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters.

Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a protein present at high levels in breast cyst fluid, has been measured in 104 breast tumour cytosols by using an immunoenzymatic assay. Concentrations of Zn-alpha 2-gp ranged from 0 to 23.5 micrograms/mg of total soluble protein, with an average value of 2.4 micrograms/mg. There was no significant correlation between Zn-alpha 2-gp and menopausal status, tumour size or lymph node involvement, or between this protein and biochemical parameters such as oestrogen receptor, cathepsin D or pS2 levels. However, there was a significant association between Zn-alpha 2-gp and histological grade of tumours, with higher Zn-alpha 2-gp levels in well-differentiated tumours (mean 4.6 micrograms/mg) than in moderately (1.8 micrograms/mg) or poorly (0.9 micrograms/mg) differentiated tumours. On the basis of these results, we propose that Zn-alpha 2-gp may be considered as a biochemical marker of differentiation in breast cancer.

Cholesterol and apolipoprotein D in gross cystic disease of the breast.

Cholesterol and apolipoprotein D (apo D) concentrations were measured in cyst fluids and sera from 66 women with gross cystic disease of the breast. Intracystic cholesterol concentrations are about twofold greater than those found in serum, whereas apo D, the major cyst fluid protein, is present in concentrations as much as 1000-fold greater than found in serum. We classified the cyst fluids into two groups by K+/Na+ ratio and albumin concentration and measured intracystic cholesterol and apo D concentrations in each group. Type I cysts had an average content of cholesterol (12.7 mmol/L) moderately lower than that in Type II cysts (17.6 mmol/L). By contrast, the average concentration of apo D in Type I cyst fluids (15.1 g/L) was slightly higher than that in Type II cysts (13.7 g/L). The absence of a correlation between cholesterol concentration and apo D concentration and the results from previous binding analysis suggest that this protein is not involved in the accumulation of cholesterol in breast-cyst fluid.

Factors affecting protein composition of breast secretions from nonlactating women.

Breast secretions can be classified into two types according to their major protein components. Type I fluids contain Zn-alpha 2-glycoprotein, apolipoprotein D, and gross cystic disease fluid protein-15, while Type II fluids are characterized by the presence of lactoferrin, lysozyme, and alpha-lactalbumin. In this study, the polypeptide composition of breast secretions from 719 nonlactating women was evaluated by using polyacrylamide gel electrophoresis. The required amount for the analysis (1 microliter) was obtained from 50% of control women and from 75% of women with mammary disease. There were more secretors in premenopausal than in postmenopausal women, as well as in parous than in nulliparous women. Evaluation of factors affecting protein composition of breast secretions revealed that Type II fluids were found in the majority of women who had given birth in the last four years and in a high proportion of oral contraceptive users. After excluding both of these groups, Type II fluids were detected in 47% of patients with breast cancer, but only in 8% of control women and in 16% of women with benign breast diseases. Taken together, these results suggest that protein analysis of breast secretions could be an useful tool for the study of breast pathologies.

Identification of the major protein components in breast secretions from women with benign and malignant breast diseases.

The protein composition of breast secretions from 99 premenopausal women with benign or malignant breast diseases and from 70 control women without breast pathologies has been studied by using polyacrylamide gel electrophoresis. These fluids have been classified into two types according to their major polypeptide components. Type I fluids are defined by three major distinctive bands at Mr 44,000, 24,000, and 17,000, while those designated Type II present distinctive bands at Mr 80,000, 15,000, and 14,000. Amino acid sequencing and immunoblotting analysis demonstrated that proteins in Type I secretions correspond to Zn-alpha 2-glycoprotein, apolipoprotein D, and gross cystic disease fluid protein-15, while those from Type II fluids have been identified as lactoferrin, lysozyme, and alpha-lactalbumin. Most women (93%) without breast pathology and most patients (88%) with benign diseases had secretions with a Type I polypeptide pattern. By contrast, a large percentage (57%) of secretions from women with breast carcinoma presented a Type II protein pattern. Further studies with a large number of women will be useful for corroborating the potential clinical interest of breast fluid protein analysis.