Maria L Carcangiu

Publications (6)18.23 Total impact

• Article: Shed HER2 extracellular domain in HER2-mediated tumor growth and in trastuzumab susceptibility.

  Gaia C Ghedini, Valentina Ciravolo, Monica Tortoreto, Sarah Giuffrè, Francesca Bianchi, Manuela Campiglio, Mimosa Mortarino, Mariangela Figini, Angela Coliva, Maria L Carcangiu, Milvia Zambetti, Tiziana Piazza, Silvano Ferrini, Sylvie Ménard, Elda Tagliabue, Serenella M Pupa
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  ABSTRACT: The question of the serum HER2 extracellular domain (HER2/ECD) measurement for prediction of response to the anti-HER2 antibody Trastuzumab is still an open and current matter of clinical debate. To elucidate the involvement of shed HER2/ECD in HER2-driven tumor progression and in guiding therapy of individual patients, we examined biological effects exerted by elevated HER2/ECD in cancer growth and in response to Trastuzumab. To this purpose SKOV3 tumor cells were stably transfected to release a recombinant HER2/ECD molecule (rECD). Transfectants releasing high levels of 110-kDa rECD, identical in size to native HER2/ECD (nECD), grew significantly slower than did controls, which constitutively released only basal levels of nECD. While transmembrane HER2 and HER1 were expressed at equal levels by both controls and transfected cells, activation of these molecules and of downstream ERK2 and Akt was significantly reduced only in rECD transfectants. Surface plasmon resonance analysis revealed heterodimerization of the rECD with HER1, -2, and -3. In cell growth bioassays in vitro, shed HER2 significantly blocked HER2-driven tumor cell proliferation. In mice, high levels of circulating rECD significantly impaired HER2-driven SKOV3 tumor growth but not that of HER2-negative tumor cells. In vitro and in mice, Trastuzumab significantly inhibited tumor growth due to the rECD-facilitated accumulation of the antibody on tumor cells. Globally our findings sustain the biological relevance of elevated HER2/ECD levels in the outcome of HER2-disease and in the susceptibility to Trastuzumab-based therapy.
  Journal of Cellular Physiology 10/2010; 225(1):256-65. · 3.87 Impact Factor
• Article: Hysteroscopy in endometrial cancer: new methods to evaluate transtubal leakage of saline distension medium.

  Eugenio Solima, Valentina Brusati, Antonino Ditto, Shigeki Kusamura, Fabio Martinelli, Francesco Hanozet, Maria L Carcangiu, Marco Maccauro, Francesco Raspagliesi
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  ABSTRACT: This study was undertaken to evaluate transtubal fluid leakage after low pressure office saline solution hysteroscopy. Forty stage I/II endometrial cancer patients were submitted to office hysteroscopy at the National Cancer Institute of Milan. Uterine cavity was distended by a 1000-mL saline solution bag, placed 50 cm above the patient's plane. After visualization of uterine cavity, a radiotracer (technetium Tc 99m) and patent blue dye were injected subendometrially. During the staging surgery peritoneal free fluid was analyzed to detect patent blue dye, technetium Tc 99m or free cancer cell by cytologic examination. Technetium Tc 99m and patent blue dye were detected on the peritoneal surface and in the peritoneal fluid in 2 patients. In 1 of these peritoneal cytology was negative for cancer cells. Peritoneal cytology was positive in 2 cases. The risk of transtubal fluid leakage during hysteroscopy is absent when performed with intrauterine pressure less than 40 mm Hg. Transtubal fluid leakage is not a synonym of cancer cell dissemination.
  American journal of obstetrics and gynecology 03/2008; 198(2):214.e1-4. · 3.28 Impact Factor
• Article: Incidental carcinomas in prophylactic specimens in BRCA1 and BRCA2 germ-line mutation carriers, with emphasis on fallopian tube lesions: report of 6 cases and review of the literature.

  Maria L Carcangiu, Bernard Peissel, Barbara Pasini, Gianbattista Spatti, Paolo Radice, Siranoush Manoukian
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  ABSTRACT: The identification of germ-line mutations in 2 genes (BRCA1 and BRCA2) responsible for the majority of hereditary ovarian cancers has led an increasing number of women carriers of these mutations to undergo prophylactic oophorectomy (PO) to reduce their risk of subsequent ovarian carcinoma. A large number of unexpected, clinically occult neoplasms are thus being discovered. Up to December 2004, the Medical Genetics Service of the National Cancer Institute in Milan, Italy, has tested 756 probands from breast and/or ovarian cancer families for BRCA1 and BRCA2 germ-line mutations. Molecular screening of family members led to the identification of 344 female carriers of BRCA1 (239) or BRCA2 (105) germ-line mutations. Of the 186 potentially eligible women (37 of whom had tested positive for BRCA1 and 13 for BRCA2 mutation), 50 (26.8%) chose to undergo PO. Six clinically occult primary gynecologic malignancies (2 stage IIIC serous carcinomas of the ovary, 3 in situ serous carcinomas of the fallopian tube, and 1 stage IIB invasive serous carcinoma of the fallopian tube) and 1 occult ovarian metastasis from breast carcinoma were identified in the PO specimens of 7 women (all BRCA1 mutated). Four of the patients with occult primary gynecologic cancers are alive without disease 129, 87, 38, and 7 months after PO, respectively. One of the 2 patients with primary ovarian cancer and the single patient with tubal invasive carcinoma are alive with recurrent disease 83 and 20 months after PO, respectively. In addition, one of the patients whose PO specimen did not show any malignancy presented with stage IIIC tubal carcinoma 77 months after PO. The relatively high number of tubal neoplasms found at PO in this group of patients underlines the linkage between mutation and the risk of developing tubal cancer, and stresses the need to include removal of the entire tubes at the time of PO and of thoroughly evaluating the specimens at the microscopic level. The upstaging of all 3 invasive carcinomas after staging surgery, and the late recurrence and persistence of 2 of them despite treatment indicate that small size of the tumors should not preclude therapy.
  American Journal of Surgical Pathology 11/2006; 30(10):1222-30. · 4.35 Impact Factor
• Article: Atypical epithelial proliferation in fallopian tubes in prophylactic salpingo-oophorectomy specimens from BRCA1 and BRCA2 germline mutation carriers.

  Maria L Carcangiu, Paolo Radice, Siranoush Manoukian, Gianbattista Spatti, Morena Gobbo, Valeria Pensotti, Rosella Crucianelli, Barbara Pasini
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  ABSTRACT: Although growing numbers of tubal carcinomas in carriers of BRCA1 and BRCA2 germline mutations have been reported, very little is known about the nature and frequency of their possible precursor lesions. The aim of this study is to investigate the occurrence of atypical proliferative tubal lesions in grossly normal fallopian tubes from 26 women with BRCA1 and BRCA2 germline mutations who underwent prophylactic salpingo-oophorectomy and whose ovaries were histologically negative for carcinoma. Fallopian tubes from 49 women who had undergone hysterectomy with salpingo-oophorectomy for uterine leiomyoma served as controls. In the 22 BRCA1-mutated women, there were two in situ carcinomas and two atypical hyperplasias of the tubal epithelium. The tubes of the BRCA2-mutated women and of the 49 control women did not show any atypical proliferation. The frequency of proliferative lesions of the tubal epithelium, including in situ carcinoma, appears to be increased in BRCA1 mutation carriers. Removal and thorough examination of the fallopian tubes at the time of surgical prophylaxis for ovarian cancer is therefore recommended.
  International Journal of Gynecological Pathology 02/2004; 23(1):35-40. · 1.45 Impact Factor
• Article: Microinvasive squamous cell cervical carcinoma.

  Francesco Raspagliesi, Antonino Ditto, Eugenio Solima, Pasquale Quattrone, Rosanna Fontanelli, Flavia Zanaboni, Francesco Hanozet, Gianbattista Spatti, Enrico Calabrese, Maria L Carcangiu
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  ABSTRACT: Several histologic tumor-related features are the key factors for further treatment planning in microinvasive cervical cancer (MIC) after conization. To better define the indications for conservative treatment of MIC we conducted a literature review for prognostic factors for MIC and we carried out a prospective observational study evaluating most important pathologic factors and the relationships between tumor and edges of the cone and incidence of recurrences. In our experience seven recurrences were observed. Two distinct groups of patients were identified with a clearance lower or higher of 10 and 8 mm for apical and lateral margin respectively. Depth of infiltration and even lymph-vascular involvement have been confirmed as the most important histologic parameters to be evaluated. Apical and lateral clearance of the tumor are significantly correlated with the recurrence rate. If an adequate lateral border of healthy tissue is present on the specimen, conization may be considered as definitive treatment of MIC.
  Critical Reviews in Oncology/Hematology 01/2004; 48(3):251-61. · 4.41 Impact Factor
• Article: Nerve-sparing radical hysterectomy: a pilot study.

  Francesco Raspagliesi, Antonino Ditto, Shigeki Kusamura, Rosanna Fontanelli, Gianbattista Spatti, Eugenio Solima, Flavia Zanaboni, Maria L Carcangiu
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  ABSTRACT: Nerve-sparing radical hysterectomy has increasingly been used for cervical cancer, with less morbidity. We aimed with this study: i) to describe an alternative technique of nerve-sparing radical Piver III hysterectomy, using the CUSA, in which attention was given to the uterosacral ligament and cardinal ligament; ii) to evaluate the feasibility of this new nerve-sparing technique; iii) to describe the surgical anatomy of the autonomic nervous system; iv) to assess the early incidence of bladder dysfunction. Twelve consecutive patients with local-regional advanced cervical cancer were enrolled in the study on nerve-sparing radical hysterectomy with extended pelvic lymphadenectomy. The mean age was 44 years (range, 30-59), mean body mass index was 24 kg/m2 (range, 18-30), mean operating time was 217 mins (range, 195-240), and mean blood loss was 437 cc (range, 200-750). The average hospitalization time was 9 days (range, 5-15 days). Two patients presented pathologically positive parametrium. Two of 12 (17%) patients were discharged with self-catheterism. In the first outpatient follow-up, 1 patient had recovered spontaneous voiding. The nerve-sparing technique with CUSA can be an option to reduce radical hysterectomy-related morbidity. The technique proved to be feasible, with promising results in terms of preventing bladder dysfunction. An elevated body mass index and large tumors can impair the performance of the technique. Further studies clarifying neuroanatomy and neurophysiology of autonomic nervous structures, as well as a prospective controlled trial on nerve-sparing radical hysterectomy should be carried out to confirm our data.
  Tumori 89(5):497-501. · 0.86 Impact Factor