Low CD10 mRNA Expression Identifies High-Risk Ductal Carcinoma In Situ (DCIS)

PURPOSE: Optimal management of breast ductal carcinoma in situ (DCIS) is controversial, and many patients are still overtreated. The local death of myoepithelial cells (MECs) is believed to be a pre-requisite to tumor invasion. We thus hypothesized that loss of CD10 expression, a MEC surface peptidase, would signify basement membrane disruption and confer increased risk of relapse in DCIS. The aim of our study was to retrospectively evaluate the prognostic value of CD10 in DCIS. EXPERIMENTAL DESIGN: CD10 expression was evaluated by quantitative RT-PCR and immunohistochemistry using paraffin-embedded samples of normal breast tissue (n = 11); of morphologically normal ducts associated with DCIS (n = 10); and of DCIS without an invasive component (n = 154). RESULTS: CD10 immunostaining was only observed in MECs in normal tissue and in DCIS. Normal tissue showed high mRNA expression levels of CD10, whereas DCIS showed a variable range. After a median follow-up of 6 years, DCIS with CD10 expression below the levels observed in normal tissue (71%) demonstrated a higher risk of local relapse (HR = 1.88; [95CI:1.30-2.70], p = 0.001) in univariate analysis. No relapse was observed in patients expressing high CD10 mRNA levels (29%) similar to the ones observed in normal tissue. In multivariate analysis including known prognostic factors, low CD10 mRNA expression remained significant (HR = 2.25; [95%CI:1.24-4.09], p = 0.008), as did the recently revised Van Nuys Prognostic Index (VNPI) score (HR = 2.03; [95%CI:1.23-3.35], p = 0.006). CONCLUSION: The decrease of CD10 expression in MECs is associated with a higher risk of relapse in DCIS; this knowledge has the potential to improve DCIS management

Troubles neurologiques compliquant une néoplasie du col utérin

A 47-year-old patient is admitted to the hospital for visual disorders and paresthesia on her left hemiface and her superior left limb. Symptoms appeared about a month before. The patient is currently under treatment for a non metastatic cervical adenocarcinoma, of stage IIIb according to FIGO. Further exams show bilateral hypodense cerebral lesions of unknown origin despite many complementary tests, among which a transthoracic and transoesophageal echocardiography, autoimmune and infectious testings. During her hospitalisation, the patient's condition worsens on the neurologic and cardiac levels in spite of a wide-spectrum empirical antibiotherapy initiated with the presumed diagnosis of infectious endocarditis. The repetition of cardiac echocardiographies ends up showing a nodule on the mitral valve. The context of neoplasia, negative hemocultures and serologies, lead us to evoke the diagnostic of marantic endocarditis even though this kind of complication was rarely described in cases of cervical neoplasia. An anticoagulant treatment is therefore initiated and the patient's state will progressively improve, at least at first.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Assessment of circulating dickkopf-1 with a new two-site immunoassay in healthy subjects and women with breast cancer and bone metastases

The aim of our study was to investigate the sex- and age-related changes of serum Dickkopf-1 (Dkk-1), a soluble inhibitor of the Wnt signaling pathway, in healthy individuals and in patients with breast cancer (BC) and bone metastases (BM) using a new ELISA. Association of serum Dkk-1 with markers of bone turnover was also investigated. Serum Dkk-1 measurements were performed using a commercial sandwich ELISA in 150 healthy men, 175 healthy pre- and postmenopausal women (20-65 years), 22 women with BC and BM (mean age 63 years), and 16 women with BC and metastases at sites other than bone (mean age 53 years). Intra- and interassay coefficients of variation were below 7% and 12%, respectively. The detection limit was determined to be 0.018 microg/L. In healthy women and men, Dkk-1 did not change with age. Serum Dkk-1 modestly correlated with serum bone alkaline phosphatase (r = 0.19, P = 0.013) and serum C-terminal cross-linking telopeptide of type I collagen (r = 0.19, P = 0.014) in women but not in men. Dkk-1 levels were higher in women with BC and BM (5.57 +/- 5.50 microg/L) than in healthy age-matched controls (3.47 +/- 1.47 microg/L, P < 0.0001) and women with metastases at sites other than bone (3.57 +/- 1.66 microg/L, P = 0.0003). In conclusion, serum Dkk-1 is stable with age in healthy women and men and increases in patients with BC and BM. Measurements of circulating Dkk-1 with this new ELISA may be useful for the clinical investigation of patients with malignant bone diseases.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

CD10 expression and clinical outcome.

<p>(A) scatter plot of CD10 expression evaluated by qRT-PCR for normal (N = 11) and DCIS (N = 154) samples. All normal samples and one-third of the DCIS were considered CD10 positive. (B) Kaplan-Meier curves of disease-free survival for patients with DCIS (N = 154) according to CD10 mRNA expression by qRT-PCR expression. (C) Kaplan-Meier curves of disease-free survival for patients with DCIS treated by tumorectomy only or tumorectomy and radiation (N = 77) according to CD10 mRNA expression by qRT-PCR expression.</p

Combined CD10 and VPNI risk.

<p>(A) Cross-tabulation between CD10 qRT-PCR expression and VNPI score. (B) Disease-free survival analysis for patients with DCIS according to CD10 mRNA expression by qRT-PCR combined with VNPI risk group.</p

CD10 immunostaining of the myoepithelial cell (MECs) layer (original magnification <b>×</b>200).

<p>(A) intense staining (3) and a circumferential membrane expression (3) observed on normal breast (score = 6); (B) intense staining (3) and a circumferential membrane expression (3) observed on DCIS (score = 6); (C) intermediate staining (2) and partial membrane expression (2) observed on DCIS (score = 4); (D) weak staining (1) and focal membrane expression (1) observed on DCIS (score = 2).</p