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Publications and source records attributed to A M Merino.
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BACKGROUND: Here we evaluate the expression and prognostic value of lysozyme, a milk protein that is also synthesized by a significant percentage of breast carcinomas, in women with breast cancer. METHODS: Lysozyme expression was examined by immunohistochemical methods in a series of 177 breast cancer tissue sections. Staining was quantified by using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. The prognostic value of lysozyme was retrospectively evaluated by multivariate analysis that took into account conventional prognostic factors. RESULTS: A total of 126 of 177 carcinomas (69.4%) stained positive for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Lysozyme values were higher in well-differentiated and moderately differentiated tumors than in poorly differentiated tumors (P < .05). Similarly, lysozyme levels were higher in small and node-negative tumors than in large and node-positive tumors (P < .05). Moreover, results indicated that low lysozyme content predicted shorter relapse-free survival and overall survival (P < .005). Separate Cox multivariate analysis in subgroups of patients as defined by node status showed that lysozyme expression was an independent prognostic factor able to predict both relapse-free survival and overall survival in node-negative patients (P < .05). CONCLUSIONS: Tumoral expression of lysozyme is associated with lesions of favorable evolution in breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer.
BACKGROUND: In this study we evaluated the expression and clinical significance of pepsinogen C, an aspartic proteinase involved in the digestion of proteins in the stomach, in patients with gastric cancer. METHODS: Pepsinogen C expression was examined by immunohistochemical methods in a series of 95 gastric carcinomas. The prognostic value of pepsinogen C was retrospectively evaluated by multivariate analysis taking into account conventional prognostic parameters. Follow-up period of patients was 21.4 months. RESULTS: A total of 25 (26.3%) gastric carcinomas stained positively for pepsinogen C. The percentage of pepsinogen C-positive tumors was higher in well-differentiated (50%) than in moderately differentiated (19.5%) and poorly differentiated (21.9%) tumors (P < .05). Similarly, significant differences in pepsinogen C immunostaining were found between node-negative and node-positive tumors (47.1% vs. 14.7%; P < .001). In addition, statistical analysis revealed that pepsinogen C expression was associated with clinical outcome in gastric cancer patients. Low pepsinogen C levels predicted short overall survival periods in the overall group of patients with gastric cancer (P < .001), and in 71 patients with resectable carcinomas (P < .005). Multivariate analysis according to Cox's model indicated that pepsinogen C immunostaining was an independent predictor of outcome for both overall and resectable gastric cancer patients (P < .05, for both). CONCLUSIONS: The expression of pepsinogen C in gastric cancer may represent a useful biological marker able to identify subgroups of patients with different clinical outcomes.
BACKGROUND: Male breast cancer (MBC) is a rare tumor in comparison to the same disease in the female population (FBC). Classical prognostic factors (tumor size, node status, estrogen receptor positivity, histological grade) have a similar prognostic value in both tumors, but MBC seems to have a worse outcome. Several markers under estrogen control have been shown with a similar incidence in breast tumors of both sexes, while androgen-induced markers have been detected in a higher percentage of breast tumors in males. AIMS AND METHODS: Our purpose was to compare in 68 MBC and in 68 FBC the expression of Pepsinogen C (Pep C) and Apolipoprotein D (Apo D), two proteins under androgen control, by immunohistochemical methods. RESULTS: Pep C was expressed by 52 of 68 (76.4%) MBC patients, whereas 34 of 68 (50%) FBC showed positive staining. Apo D was expressed by 57 of 68 (83.8%) MBC patients, while 40 of 68 (41.2%) FBC stained positively. Differences between percentages of positive expression were significant (p<0.005 for Pep C; p<0.0001 for Apo D). Moreover, differences between expression levels of Pep C and Apo D in both populations of patients were significant. The mean value of Pep C was significantly higher in male breast tumors (HSCORE = 141.3) than in the females (HSCORE = 80.3) (p<0.0001). Similarly, Apo D mean value was significantly higher in MBC (HSCORE = 161.5) than in FBC (HSCORE = 102.3) (p=0.006). CONCLUSION: These differences can open the field of a more selective hormonal therapy that should not be based on estrogen receptor status only, but also on androgen receptor status.
BACKGROUND: Apolipoprotein D is a glycoprotein of the human plasma whose functional role remains unclear. On the other hand, this protein is also produced by breast carcinomas and is positively associated with a favorable outcome of patients. However, none study has focused on metastasic lesions. AIM: To analyze apolipoprotein D expression in breast cancer patients and their synchronous metastasic axillary lymph nodes. METHODS: We analyzed by immunohistochemical assay both, the tumoral expression of apolipoprotein D in primary tumors and in their synchronous metastasic axillary lymph nodes of 30 node-positive breast cancer patients. RESULTS: Of the primary tumors, 28 (93.3%) showed a positive immunostaining for apolipoprotein D, although there was wide variability immunostaining values. On the other hand, 16 (53.3%) patients showed a positive immunostaining for the protein in their tumoral lymph nodes. In addition, there was a significant positive relationship between the tumoral expression of apolipoprotein D in primary tumors and metastasic lymph nodes (P < 0.05). However, only immunostaining values of the protein in primary tumors achieve statistical signification (P < 0.05) as prognostic factor of favorable evolution to predict overall survival from patients. CONCLUSIONS: Apolipoprotein D is also expressed in metastasic lymph nodes of breast carcinomas, but with a different pattern of immunostaining and less clinical significance than in primary tumors.
BACKGROUND: Apolipoprotein D (ApoD), a protein component of the human plasma lipid transport system, is an androgen regulated protein in both breast and prostate cancer cell lines. METHODS: Here we examined, by immunohistochemical assay, the ApoD expression in normal, benign and malignant prostate tissues. RESULTS: ApoD was detected in the two analyzed normal prostate tissues, in 16 (94.1%) of 17 benign prostatic hyperplasias, and in 36 (63.1%) of 57 prostate carcinomas. In prostate carcinomas, ApoD immunostaining values did not show significant relationship neither with age of the patients, stage and histologic grade of the tumors, nor with preoperative serum levels of prostatic specific antigen (PSA). However, ApoD-negative immunostaining predicted shorter survival duration in the subgroup of 46 patients with nonresectable prostate cancer (p = 0.02). CONCLUSIONS: Our results led us to consider that Apo D expression by prostate carcinomas migth be of clinical usefulness for identificating lesions with different evolution.
Pepsinogen C is a proteolytic enzyme involved in the digestion of proteins in the stomach; it is also synthesized by a significant percentage of female breast carcinomas. In addition, it has been demonstrated that pepsinogen C is one of the few proteins induced by androgens in breast carcinoma cells. Here we evaluate the expression of pepsinogen C by immunoperoxidase staining in normal breast tissue from 3 male patients, 15 gynecomastia tissues, 2 male in situ breast carcinomas, and 68 male invasive breast carcinomas. Pepsinogen C immunostaining values were quantified in male breast tumors using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. The results indicated positive immunohistochemical staining for pepsinogen C in all gynecomastia tissues, the two in situ ductal carcinomas, and 52 of 68 invasive breast carcinomas (76.4%). The three normal breast tissues analyzed showed negative staining for pepsinogen C, whereas invasive tumors showed clear differences among them with regard to the intensity and percentage of staining cells. In addition, pepsinogen C scores were significantly higher in well-differentiated (grade I, 188.7) and moderately differentiated (grade II, 145.8) tumors than in poorly differentiated (grade III, 98.5) tumors (p = 0. 032). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (158.5 vs. 44.3, respectively; p = 0.009). Patients with pepsinogen C-positive tumors reached longer relapse-free and overall survival periods than did those with tumors with negative staining, but no statistical differences were observed between survival curves calculated for these two groups of patients. This results demonstrate expression of pepsinogen C by gynecomastias and by a high percentage of male breast carcinomas and may indicate an important role of pepsinogen C in the pathophysiology of male breast diseases.
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.
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.
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.
An aspartic proteinase present in cyst fluid from women with gross cystic breast disease was purified by a procedure involving affinity chromatography on pepstatin-agarose and size-exclusion high performance liquid chromatography. The amino-terminal sequence of the purified breast proteinase was identical to that corresponding to gastric pepsinogen C. Additional data on cleavage specificity, pH optimum, and immunological properties supported the close relationship between both molecules. Northern blot analysis and polymerase chain reaction amplification studies performed on RNAs obtained from normal and pathological breast tissues demonstrated that the protein is produced by mammary carcinomas and cysts, but not by the normal resting mammary gland. Immunohistochemical staining of paraffin-embedded tissue sections confirmed the existence of a subset of tumors that have the ability to synthesize and secrete this pepsin zymogen. On the basis of these results, we suggest that pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases, being also of potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies.
We have examined by immunohistochemistry the ability of human carcinomas of various origin to produce pepsinogen C, an aspartyl proteinase mainly involved in the digestion of proteins in the stomach and recently found to be associated with breast carcinomas. Of the 268 tumors analyzed 80 (29.8%) showed positive staining for pepsinogen C. These positive tumors included 12 gastric (38.7% of the 31 examined cases), nine pancreatic (42.8%), two renal (20%), 12 prostatic (40%), three bladder (27.3%), 14 endometrial (29.7%) and 18 ovarian (40%) carcinomas. We also detected 10 melanomas (50%) that were positive for pepsinogen C. By contrast, immunohistochemical staining for the proteinase was not detected in colorectal, cervical, lung and basal cell skin carcinomas. These results demonstrate that pepsinogen C, a proteolytic enzyme of highly restricted expression in human tissues, can also be expressed by a wide variety of human carcinomas. In addition, and similar to pepsinogen C expression in breast carcinomas, the production of this enzyme by different human tumors might be related to putative hormonal alterations associated with the development and progression of these tumors.
BACKGROUND: The aim of this study was to evaluate the pepsinogen C expression in malignant cutaneous melanomas and analyze its possible relationship to clinical and pathological parameters. Pepsinogen C is an aspartyl proteinase primarily involved in the digestion of proteins in the stomach and represents one of the main androgen-inducible proteins in breast cancer cells. METHOD: Tumoral pepsinogen C expression was retrospectively analyzed in 35 paraffin-embedded tissues from patients with primary malignant cutaneous melanoma and in 10 samples from 10 benign lesions (4 dermal melanocytic nevi, 4 compound melanocytic nevi and 2 dysplastic melanocytic nevi), using immunohistochemical methods. RESULTS: The benign lesions were consistently negative for pepsinogen C, whereas 20 of the 35 malignant melanomas (57%) showed positive immunostaining for pepsinogen C. The percentage of pepsinogen C-positive tumors was significantly higher in men than in women (p=0.01) and in epithelioid melanomas than in fusocellular or mixed type melanomas (p=0.003). In addition, the percentage of pepsinogen-C positive tumors was positively and significantly correlated with lesion thickness (p=0.003), Clark's level of invasion (p=0.028) and tumor stage (p<0.001). CONCLUSION: Pepsinogen C could be a new prognosticator of unfavorable outcome in cutaneous malignant melanoma.
Pepsinogen C is an aspartyl protease mainly involved in the digestion of proteins in the stomach, and an androgen-inducible protein in breast cancer cells. The aims of this study were to evaluate the expression and clinical significance of this enzyme in the primary tumors of prostate cancer patients with bone metastasis who were scheduled to receive antiandrogenic therapy. This study was prospectively performed in 28 stage D2 prostate cancer patients who, after diagnosis, received maximum androgen blockade. Pepsinogen C tumor expression was analyzed in samples (24 from needle biopsy cylinders and four from transurethral resection specimens) from primary tumors using an immunohistochemical assay. Twelve prostate carcinomas (42.8%) were positive for pepsinogen C. Pepsinogen C was a significant prognostic factor to predict a longer overall survival in the patients of our study (p<0.01). Pepsinogen C can be a new prognostic factor and a useful biological marker of androgen dependency in prostate cancer.