[Clinicopathologic features of mammary microglandular adenosis with carcinoma: a study of 5 cases].

Objective: To study the clinicopathologic, immunohistochemical features, differential diagnoses and prognosis of mammary microglandular adenosis with carcinoma (MGACA) with micropapillary pattern. Methods: Five cases of MGACA were collected from 2010 to 2016 and reviewed for their clinical, histologic features and outcome.EnVision method were done for S-100 protein, cytokeratin (CK), p63, Calponin, smooth muscle myosin heavy chain (SMMHC), PR, ER and HER2. Results: Histologically, microglandular adenosis(MGA), atypical MGA (AMGA) and invasive carcinoma were seen in all five cases of MGACA. The invasive component was metaplastic carcinoma in one case and ductal in four cases. All epithelial cells were S-100 and CK positive in MGA, AMGA and invasive carcinoma. p63, Calponin and SMMHC negativity confirmed the lack of a myoepithelial cell layer in MGA, AMGA and MGACA. PR was weakly focally positive in one case, but ER and HER2 were negative in all cases (four cases were triple negative). Ki-67 index was 20% to 40%. Laminin and collagen Ⅳ staining showed the presence of basement membrane in MGA and AMGA, except MGACA. The follow-up time ranged from 3 months to 6 years, and all patients were alive without recurrence or distant metastasis. Conclusions: MGACA is a rare tumor with distinct morphological and IHC features. Compared to most triple-negative breast cancers, MGACA seems to have a relatively favorable outcome.

CD10 Immunohistochemical Expression in Apocrine Lesions of the Breast.

OBJECTIVE: In the breast, CD10 is expressed by myoepithelial cells (MECs), and apocrine metaplasia has also been mentioned as being positive with this marker. Apocrine lesions have been explored for the expression of CD10. METHODS: The apocrine lesions studied included 11 cysts, 6 cases of apocrine adenosis, 2 of apocrine metaplasia or hyperplasia in papilloma, 13 ductal carcinomas in situ (DCIS) and invasive carcinomas (14 ductal and 4 lobular). RESULTS: Benign apocrine lesions showed complete or partial luminal CD10 staining, although most cases included parts without staining, and 2 lesions were completely negative. The MECs were often but not always positive. Nine of the 13 cases of apocrine DCIS displayed no luminal staining, but 4 demonstrated very focal luminal positivity. The MECs around the DCIS showed a spectrum of staining from nil to strong and complete. Only 4 invasive carcinomas demonstrated luminal/membranous staining. Cytoplasmic CD10 positivity was seen focally in 4 invasive cancers and in 3 DCIS. CONCLUSION: CD10 positivity is luminal/membranous in most benign apocrine lesions, the staining being nonuniversal and sometimes focal. Analogous staining in apocrine malignancies seems rarer in DCIS and even rarer in invasive apocrine carcinomas, but atypical cytoplasmic positivity may also occur. CD10 is not an ideal myoepithelial marker in apocrine lesions.

IgG4-related sclerosing disease of the breast successfully treated by steroid therapy.

IgG4-related sclerosing disease was first identified and defined in the twenty-first century. In this pathology, the serum IgG4 level increases and IgG4-positive plasma cells and lymphocytes infiltrate organs such as the pancreas, salivary glands, lacrimal glands, kidneys, and the retroperitoneum. Presented in this report is a case of IgG4-related sclerosing disease that occurred in the breast and was treated successfully with steroid therapy. A 51-year-old woman presented with bilaterally swollen eyelids and an elevated serum IgG4 concentration. Screening CT revealed a lesion in her right breast but no other lesions. Mammography, ultrasonography, and MRI could not rule out malignancy, so a core needle biopsy was performed. Histologically, the lesion was composed of papilloma with fibrosis, adenosis, and severe lymphoplasmacytic infiltration. No malignant features were observed. Many plasma cells within the lesion were immunohistochemically positive for IgG4. IgG4-related sclerosing disease of the breast was diagnosed, and steroid therapy was initiated. During 4 weeks of steroid treatment the lesion became smaller in size, and at 7-months follow-up the lesion showed no new growth. Since steroid therapy is effective for this disease, IgG4-related sclerosing disease should be considered in the differential diagnosis of breast lesions in order to avoid unnecessary surgery.

Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas.

BACKGROUND: On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. METHODS: Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five) was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. RESULTS: All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. CONCLUSIONS: This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. VIRTUAL SLIDES: The virtual slides' for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892.

[Specific features of neovascularization of dysplastic invasiveness and cancer of the breast].

There are shown the results of study related to angioarchitechtonices of displastic pre-cancer outgrows, fibroadenoma and carcinoma of the breast (non-proliferative and proliferative forms of fibro-cystic disease - 35 cases, fibroadenoma - 32 cases, cancer - 55 cases) using histological (hematoxylin and eosin and picrofuxin staining) and immunohistochemical (angiogenesis marker - CD31 and marker of proliferation - Ki67) methods. It was estimated that the character and intensity of vascularization as well as neoangiogenesis of above-named pathologic conditions and breast cancer could be determined by the differentiation of tissue structures and neoplastic cells. The microangioarxitectonics pre-cancer outgrowths and cancer of the breast is so peculiar and characteristic for each concrete case that it should be considered for morphological diagnosing and determining the tactic of treatment.

Large-needle core biopsy in atypical intraductal epithelial hyperplasia including immunohistochemical expression of high molecular weight cytokeratin: analysis of results of a single institution.

The diagnosis of atypical intraductal epithelial hyperplasia (AIDH) constitutes 6.3% of the breast core biopsies performed at our institution. Seventy-nine cases that were diagnosed as AIDH on core biopsy and went through excisional biopsy were included. Sixty-four biopsies were performed by an image-guided 11-gauge vacuum device, 11 under sonographic guidance using 14-gauge needles and 4 by a sonographically guided 11-gauge vacuum device. The histopathology of the core biopsies and the surgical excisions were reviewed. Immunohistochemistry was performed on the consecutive sections of core biopsy specimens using high molecular weight cytokeratin (HMW-CK) (DAKO-Cytokeratin, 34betaE12). At interpretation of the stain, intensity and percentage of positive cells were taken into account. The immunoprofiles of AIDH were categorized into four groups showing negative (i.e., no staining) or low-, moderate-, high-, and very high-intensity staining. Surgical excision of the 79 lesions revealed carcinoma in only 3 cases (4%)-two infiltrating carcinomas and one intraductal carcinoma-residual AIDH in 44 cases (56%), and epithelial hyperplasia or other benign lesions without atypia in 32 cases (40%). The HMW-CK stain was performed retrospectively on all of the core biopsies and 66 of them contained residual areas with AIDH for staining. Forty-nine (74%) were CK negative or stained with low intensity, but 17 cases (26%) had a moderate- to high-intensity stain. Our study showed a lower incidence of carcinoma on surgical excision following core biopsy for AIDH than other studies. The HMW-CK stain helped to characterize the nature of the intraductal proliferation and to confirm the presence of atypia, as has been previously reported, but frequently was inconclusive. The low incidence of carcinoma brings into question the need for surgical excision of all cases of AIDH diagnosed by core biopsy.

[Diabetic fibrous mastopathy: a case report]. / Mastopathie fibreuse diabétique.

Diabetic fibrous mastoplasty or diabetic fibrous breast disease is a benign condition rarely observed. First described in 1984, it can lead to misdiagnosis because it simulates breast cancer. Diabetic fibrous mastoplasty usually occurs in patients with autoimmune disorders, particularly in patients with longstanding and complicated insulin-dependent diabetes mellitus. We present a case of fibrous mastoplasty in a patient with insulin-dependent diabetes mellitus known for 17 years. The clinical and radiological features and the clinical course are illustrative. We discuss the different pathogenic theories put forward.

[Value of interleukin-8 determination in diagnosis of benign and malignant breast tumor]. / Przydatnosc oznaczania interleukiny 8 w diagnostyce lagodnych i zlosliwych nowotworów sutka.

The studies were performed in women with breast carcinoma, benign breast tumour and in a control group. Serum levels of IL-8 were determined 1-2 days before surgical procedure, according to the enzyme-linked immunosorbent assay (ELISA). Pretreatment levels of IL-8 were significantly increased in carcinoma patients in relation to the benign tumour and the control group. The frequency of increased results and absolute values of IL-8 levels showed tendency to significant increase with the stage of disease. These results suggested that IL-8 measurement may be useful in estimation of disease progression in women with breast carcinoma.

Comparison of immunoperoxidase staining of 3 different types of CD5 antibodies in a spectrum of breast lesions.

CONTEXT: We recently described a patient with chronic lymphocytic leukemia who presented with a breast carcinoma that stained positive for CD5 using a commercially available antibody (CD5-4C7, Novocastra, Newcastle upon Tyne, UK). OBJECTIVES: To study the distribution of CD5 immunoreactivity in tissue sections of a variety of benign and malignant breast lesions using the antibody CD5-4C7 and to compare the results with those obtained with 2 other commercially available CD5 antibodies (CD5/54/F6, Dako, Ely, Cambridgeshire, UK, and CD5/54/B4, Novocastra). DESIGN: Paraffin sections of 102 breast biopsy specimens with various diagnoses were examined using the avidin-biotin immunoperoxidase complex technique. SETTING: The histopathology department of a tertiary referral teaching hospital. RESULTS: The staining results obtained with CD5-4C7 were different from those obtained with the other 2 antibodies. With 4C7, the normal and benign biopsy specimens showed varying numbers of positive epithelial cells and lymphocytes. Heterogeneous positive staining was also present in 47 (78%) of 60 invasive female breast carcinomas and in all 3 male breast carcinomas examined. A statistically significant correlation was found between CD5 positivity and tumor grade, with grade 3 tumors being less likely to be CD5 positive than grades 1 and 2 (P =.0035). No correlation was found between CD5 positivity and patient's age, tumor histologic type, axillary lymph node status, or progesterone receptors. On the other hand, the CD5/54/F6 and CD5/54/B4 antibodies only stained lymphocytes and occasional normal breast ducts, mostly those showing apocrine metaplasia. All other normal benign and malignant epithelial cells were negative. CONCLUSIONS: Positive staining for CD5 using the antibody 4C7 is seen in normal and benign breast tissue and 78% of invasive breast carcinomas. The positivity is more common in low-grade tumors. No significant staining was seen with the 2 other CD5 clones used in this study. The significance of the positive staining obtained with CD5-4C7 is not obvious, but this clone may be more sensitive than the others, or it may be recognizing an epitope shared by another antigen.

[Expression of the adhesion molecule CD44v6 in infiltrating ductal carcinomas of the breast is associated with hormone dependence. Our experience with 168 cases]. / La expresión de la molécula de adhesión CD44v6 en carcinomas ductales infiltrantes de mama se asocia con la hormonodependencia. Nuestra experiencia con 168 casos.

In order to investigate the possible hormone-dependence of CD44v6 in human breast cancer, we assayed the concentrations of this isoform in the membrane fraction of 168 invasive ductal carcinomas (IDC) and in 26 normal breast tissue samples, 18 fibradenomas (FAD), 3 fibrocystic disease specimens (FD), 7 mucinous carcinomas and 4 medullary carcinomas using the ELISA method. The results were compared with those of the estrogen (ER) and progesterone (PR) receptors, pS2, tissue type plasminogen activator (t-PA), cathepsin D, epidermal growth factor receptor (EGFR) and c-erbB2/neu oncoprotein concentrations. Menopausal status, size of the tumor in the cases of cancers, axillary lymph node involvement, histologic grade, ploidy, cellular synthesis phase, multifocality and multicentricity were also considered as variables. The cut-off value for CD44v6-positivity was set at 5 ng/mg prt. membrane protein content. 64/138 (38.1%) infiltrating ductal carcinomas scored positive. This was significantly higher than for the normal breast tissue (0/26; p: 0.0001), similar to that seen in the FAD (3/18), fibrocystic disease (0/3), infiltrating mucinous carcinomas (4/7) and lobular (3/15) and significantly lower than for the infiltrating medullary carcinomas (4/4; p: 0.027). There were no significant differences with the other groups of tissues studied. Furthermore, CD44v6-positive IDC showed significantly higher concentrations of ER, PR and cathepsin D and lower (p: 0.051) concentrations of EGFR when compared to their CD44v6-negative counterparts. The significant coexpression of ER, PR and cathepsin D seems to indicate a possible role for hormonal regulation of CD44v6 expression while the role of pS2 and t-PA, estrogen related proteins, was very reduced.

Circulating antibodies against the breast tumor marker GCDFP-15/gp17 in mammary carcinoma patients and in patients carrying benign breast conditions.

Sera samples from 111 women, including 73 breast cancer patients and 38 patients with benign diseases of the breast, were examined. These were compared with samples from healthy women or from patients carrying tumors of origin other than breast as controls. This was done to determine whether antibodies against GCDFP-15/gp17, a protein of gross cystic disease fluid also secreted by mammary apocrine tumor cells, could be found. We observed that 2.6% of mammary disease patients affected by benign conditions and 5.5% of patients carrying malignant mammary gland tumors expressed statistically significant amounts of antibodies against GCDFP-15/gp17 (p < 0.01). The highest circulating anti-GCDFP-15/gp17 antibody levels occurred in patients with highly malignant ductal or lobular carcinoma of the breast and in patients with dysplasia. No correlation was found between the presence of circulating antibodies and the size of the tumor or the age of the patients. A bimodal correlation with the percent of invaded lymph nodes was observed instead. IgM and IgG isotypes were detected among the circulating anti-GCDFP-15/gp17 antibodies, suggesting the involvement of a T-cell-mediated immunoresponse. Our findings raise the possibility that the anti-GCDFP-15/gp17 immune response may be useful as a tool for investigating some aspects of the mechanisms of breast disease progression and that GCDFP-15/gp17 may be explored as an antigen for anti-tumor vaccination. Int. J. Cancer (Pred. Oncol.) 84:568-572, 1999.

Tumour necrosis factor-alpha and interleukin-1 and -6 in fibrocystic breast disease.

The risk of developing breast cancer is higher in women presenting gross cystic disease (cysts > 3 mm in diameter) of the breast with intracystic K+/Na+ > 3 as compared with K+/Na+ < 3. The present study reports the levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) in the breast cyst fluid of women with gross cystic disease and analyses the relationship between the intracystic concentration of these cytokines, sex steroid hormones, and the K+/Na+ ratio. The concentration of these cytokines, estradiol, testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 17-OH-progesterone were determined in the breast cyst fluid of 54 women with gross cystic disease. No significant differences were found in the cystic levels of IL-1 between cysts with intracystic K+/Na+ < 3 and > 3. However, in cysts with intracystic K+/Na+ > 3 we found a lower concentration of IL-6 and TNF-alpha than in those with intracystic K+/Na+ < 3. Stepwise multiple linear regression analysis demonstrated that the concentration of IL-6 in breast cyst fluid was predicted statistically by a negative regression coefficient for the concentration of estradiol and DHEA-S, and by a positive regression coefficient for the concentration of TNF-alpha. The concentration of TNF-alpha in breast cyst fluid was predicted statistically by a positive regression coefficient for the concentration of IL-6, and by a negative regression coefficient for the concentration of estradiol. No candidate variable was included in the model to predict concentrations of IL-1 in breast cyst fluid. Our results indicate that IL-6 and TNF-alpha could have a local 'protector' role in gross cystic disease, and that they could be used as a marker to identify cyst type.

[Absence of correlation between the concentrations of carcinoembryonic antigen (CEA) and the tumor growth factor beta 2 (TGFB2) in the two main types of breast macrocysts]. / Ausencia de correlación entre las concentraciones del antígeno carcinoembrionario (CEA) y del factor de crecimiento tumoral beta 2 (TGFB2) en los dos tipos principales de macroquistes mamarios.

In order to study the possible correlation between carcinoembryonic antigen (CEA) and cellular proliferation, we assayed the concentrations of this substance in the fluid of 77 bening macrocysts of the breast classified according to their Na+/K+ ratio and compared them with those of transforming growth factor beta 2. CEA levels correlated positively and significantly with the cationic ratio, the concentrations of albumin, glucose, Cl- and pH and were higher (range: 2.5-81.5, median 12.8 vs range: 0.4-41.5, median 3.2 ng/ml (p: 0.00000) in type 2 (Na+/K+ > 3) than in type 1 (Na+/K+ < 3) cysts. There was no correlation between CEA and TGFb2, nor between the former and dehydroepiandrosterone sulphate levels. These results led us to suggest that the high CEA concentrations in type 2 cysts seem to be the consequence of loos of cellular differentiation and disruption of the cyst wall lining as well as the acquisition of embryonary properties by the latter as a consequence of a reduced hormonal microenvironment.

[Effect of running granule on repairing capacity of neuro-endocrine-immunity and DNA in treating mastoplasia].

OBJECTIVE: To explore the clinical effect and therapeutic mechanism of Runing Granule (RNG) in treating mastoplasia to elucidate its pathogenesis. METHODS: One hundred and eighty-seven patients suffering from mastoplasia were randomly divided into the RNG treated group (treated group, 147 cases), and the tabellae tamoxifen control group (control group, 40 cases). The follow-up underwent for 3 months. Before and after treatment, changes of levels of plasma neurotransmitters, serum endocrine hormone, peripheral lymphocyte unscheduled DNA synthesis, the count of T lymphocyte subsets in the luteal phase during the menstrual cycle of 104 cases were measured, their clinical effects were also observed. RESULTS: Before treatment, these cases showed disturbances in the secretion of 5-hydroxytryptamine (5-HT), epinephrine (E), estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), and the levels of norepinephrine (NE), prolactin (PRL), inducer-helper T lymphocytes (OKT4+), suppressor T lymphocytes (OKT3+), were significantly increased, progesterone (P), testosterone (T), total T cells (OKT3+), OKT4+/OKT8+ ratio, unscheduled DNA synthesis (UDS) were obviously reduced (P < 0.05, P < 0.01) in mastoplasia patients. After treatment, RNG showed regulation on disturbances of these parameters, the curative rate of the treated group was higher than that of the control group; the metabolic disturbances of 5-HT/NE, E2/P, T, OKT3+ in the treated group were improved more significantly than those in the control group (P < 0.05). During the period of clinical observation, no obvious side effect and toxicity of RNG were found. CONCLUSIONS: Mastoplasia is caused by the interactions among multi-factors in which the neuro-endocrine-immune network plays a key role in the pathogenesis of mastoplasia. RGN was effective in treating mastoplasia, the mechanism probably lays on the regulation of comprehensive coordination from the multi-layers, multi-links and multiple pathways in the neuro-endocrine-immunity network and elevation of internal environment-stabilizing capacity of the body.

[The content of DNA in the oral mucosal epitheliocytes and the expression of oncofetal antigens on the peripheral blood T-lymphocytes of women with breast dysplasias]. / Soderzhanie DNK v épiteliotsitakh slizistoi obolochki polosta rta i ékspressiia onkofetal'nykh antigenov na T-limfotsitakh perifericheskoi krovi u zhenshchin pri displaziiakh molochnykh zhelez.

The DNA content in epitheliocytes of the mucous membrane of the oral cavity and expression of carcinoembryonic antigen and trophoblast-specific beta-1 glycoprotein on peripheral blood lymphocytes, peripheral blood T-lymphocytes subsets into three groups of patients: 1--diffusion mastopathy; 2--diffusion mastopathy with fibromyoma uteri and 3--fibroadenoma were studied. It was indicated that DNA content was higher in all groups in comparison with healthy women and it was shown that in contrast to healthy women, 45% of patients studied had abnormal rate of T-cells subsets, about 30% of them had abnormal expression of CEA and TSG on peripheral blood lymphocytes. The data obtained show the significant disbalance in the mechanisms of defence and compensation taking place in the organisms of patients with nonmalignant mammary diseases.

Differential antibody reactivity and CD4 binding of the mammary tumor marker protein GCDFP-15 from breast cyst and its counterparts from exocrine epithelia.

Analysis of biopsies from breast cancer patients demonstrated that GCDFP-15 (gross cystic disease fluid protein-15) is a specific immunocytochemical marker of primary and secondary apocrine breast tumors. The protein has an amino acid sequence identical to SABP (secretory actin-binding protein), to PIP (prolactin-inducible protein) and to gp17, a protein isolated from human seminal plasma. The latter was found to bind to CD4, a T-cell co-receptor involved in antigen recognition, thereby inhibiting the ability of the receptor to interact with the HIV-1 envelope protein gp120. We compare here the ability of independently purified GCDFP-15, SABP and gp17 and of recombinant PIP both to cross-react with a panel of monoclonal antibodies (MAbs) raised against GCDFP-15 or gp17, respectively, and to bind to CD4. We show that, although the various factors share the ability to bind to the panel of antibodies used, differences in the pattern of MAb recognition can be demonstrated. By comparing the kinetic constants for binding of GCDFP-5 and gp17 to CD4 by biosensor technology, significant differences in binding affinities were observed between the 2 factors, thus reflecting structural differences. Surface plasmon resonance analysis also showed that anti-GCDFP-15 and anti-gp17 antibodies inhibit the binding of CD4 to GCDFP-15 and gp17, respectively, to different extents. Our data thus indicate that, while the various forms of the protein are encoded by the same cDNA, tissue specificities due to post-translational modifications exist. This information may be relevant for developing more sensitive and accurate tests for the use of GCDFP-15 as a diagnostic mammary tumor marker and, most importantly, raises the possibility that GCDFP-15 may constitute a breast tumor-specific antigen.

[Immunoradiometric assay of Ca 125 in breast cystic fluid]. / Dosaggio immunoradiometrico del Ca 125 nel liquido di grosse cisti della mammella.

Ca 125 was assayed in serum and in breast cyst fluid of 78 patients with GCD. Levels of the marker in cyst fluid are generally < 30 U/ml. More significative results were found in relation to cysts relapse. In apocrine cysts relapse levels were higher than 270 U/ml, in serum cysts not relapsed levels were between 31-270 U/ml. Ca 125 could have a significative role in cell differentiation and its control.

Prostate-specific antigen expression in a case of intracystic carcinoma of the breast: characterization of immunoreactive protein and literature surveys.

A case is presented of female breast intracystic carcinoma with prostate-specific antigen (PSA) expressed in high amounts in aspirated cystic fluid (55 micrograms/L). Tumor extract analysis revealed the presence of both estrogen and progesterone receptors (0.38 and 1.87 nmol/L, respectively) and high quantities of PSA too (19.52 micrograms/L). Chromatographic analysis of cystic fluid revealed two peaks of PSA, at the expected positions for free and bound serine protease. A major proportion of 33-kDa free from was also confirmed by Western blotting analysis. Free PSA was heat-stable at 56 degrees C and displayed no change after freezing-thawing. These findings are discussed in the context of a detailed literature survey. Our data support the contention that PSA immunoreactivity in intracystic fluid of breast carcinoma is partly the result of secretory activity by the neoplastic cells and that the steroid receptors can also modulate its expression.

CD44 isoforms with exon v6 and metastasis of primary N0M0 breast carcinomas.

New isoforms of CD44 with alternatively spliced exons have recently been described. Expression of exon v6 seems to be of particular interest. It has indeed been associated with poorer outcome of breast cancer patients with node invasion at diagnosis. However, no data were available for patients N0M0 (with neither metastasis nor node invasion at diagnosis). Moreover, previous statistical analyses were realized using immunohistochemical methods to detect CD44v6 expression although several variants with exon v6 have been described. We investigated expression of isoforms containing CD44v6 using an RT-PCR approach and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic samples and 52 primary breast tumors (38 invasive N0M0). Normal breasts, fibroadenomas, and cysts all express the same variant, A (with exon v6 only), while several transcripts are amplified in tumors. Expression of variants other than A correlates with acquisition of a malignant phenotype. Invasive cancers also express additional variants in comparison with in situ carcinomas. Metastasis capacities seem to be associated with transcription of variants other than A but also with no transcription of some of them, variants D (with exons v6 and v10) and L (with exons v6 to v10). Expression of variants D and L correlates with higher percentages of disease-free survival and better outcome. Expression of CD44 splice variants with exon v6, as detected by RT-PCR, might be a useful prognostic factor for breast cancer. However, since the series size is small, our results need to be confirmed by later studies on a larger number of patients.

[Levels of Cathepsin D in breast cyst fluid]. / Dosaggio della Catepsina-D nel fluido di macrocisti della mammella.

Cathepsin-D was assayed in serum and in breast cyst fluid of 60 non neoplastic patients with GCD. The results are independent from cytological type or possible cyst relapse. Although the study confirms the high levels of Cat-D in breast cyst fluid no predictive value has been demonstrated. Its expression may be related to systemic endocrine factors.