[Update on precursors of vulvar carcinoma]. / Lésions vulvaires précancéreuses : mise au point.

Vulvar carcinomas represent 4% of all gynaecological cancers with 838 new cases in France in 2018. The precursor lesions of vulvar carcinomas are differentiated vulvar intraepithelial lesion (dVIN) in a context of lichen sclerosus and vulvar high-grade squamous intraepithelial lesion (HSIL) link to human papillomavirus (HPV) infection. Three typical clinical forms of HSIL are described: the Bowenoid papulosis, the Bowen's disease and the confluent VIN. Histopathology cannot differentiate effectively these two types of lesions. P16 and P53 immunostaining are valuable tools to respectively assess HPV infection and divide different types of dVIN. However, P53 immunostaining is still lacking sensibility to detect dVIN. First line therapies are medical treatment excluding the cases with a doubt of invasion. The gold standard treatment for dVIN and vulvar HSIL are respectively topical corticosteroids and imiquimod. Primary prevention for vulvar HSIL and dVIN are respectively HPV vaccination and early treatment of lichen sclerosus. Destructive therapy can be used in case of medical treatment failure such as CO2 laser, cryotherapy, dynamic phototherapy. Surgical indications should be carefully assessed between the risk of recurrence, the spread of the lesions, the aesthetic and functional aspect. Surgical procedures consist in either superficial vulvectomy or radical vulvectomy with or without flap reconstruction. Recurrence rate after surgery is around 20%.

Estrogen-Receptor, Progesterone-Receptor and HER2 Status Determination in Invasive Breast Cancer. Concordance between Immuno-Histochemistry and MapQuant™ Microarray Based Assay.

BACKGROUND: Hormone receptor status and HER2 status are of critical interest in determining the prognosis of breast cancer patients. Their status is routinely assessed by immunohistochemistry (IHC). However, it is subject to intra-laboratory and inter-laboratory variability. The aim of our study was to compare the estrogen receptor, progesterone receptor and HER2 status as determined by the MapQuant™ test to the routine immuno-histochemical tests in early stage invasive breast cancer in a large comprehensive cancer center. PATIENTS AND METHODS: We retrospectively studied 163 invasive early-stage breast carcinoma with standard IHC status. The genomic status was determined using the MapQuant™ test providing the genomic grade index. RESULTS: We found only 4 tumours out of 161 (2.5%) with discrepant IHC and genomic results concerning ER status. The concordance rate between the two methods was 97.5% and the Cohen's Kappa coefficient was 0.89. Comparison between the MapQuant™ PR status and the PR IHC status gave more discrepancies. The concordance rate between the two methods was 91.4% and the Cohen's Kappa coefficient was 0.74. The HER2 MapQuant™ test was classified as « undetermined ¼ in 2 out of 163 cases (1.2%). One HER2 IHC-negative tumour was found positive with a high HER2 MapQuant™ genomic score. The concordance rate between the two methods was 99.3% and the Cohen's Kappa coefficient was 0.86. CONCLUSION: Our results show that the MapQuant™ assay, based on mRNA expression assay, provides an objective and quantitative assessment of Estrogen receptor, Progesterone receptor and HER2 status in invasive breast cancer.

The role of laparoscopy to evaluate candidates for complete cytoreduction of peritoneal carcinomatosis and hyperthermic intraperitoneal chemotherapy.

AIM: The aim of this study was to evaluate the role of explorative laparoscopy to evaluate candidates for complete resection of peritoneal carcinomatosis (PC) combined with hyperthermic intraperitoneal chemotherapy (HIPC). METHODS: The database of the surgical department of the Institut Gustave Roussy was used to select 113 patients planned to undergo a maximal cytoreductive surgery combined with HIPC for PC between April 2001 and July 2003. Among them, 11 underwent an explorative laparoscopy because extent of the PC was insufficiently documented to evaluate its resectability. Patient records were retrospectively reviewed. RESULTS: Laparoscopic evaluation was successful in all 11 patients. The median operating time was 38 min (range 23-75 min). The laparoscopic examinations were well tolerated in all cases. The median length of hospital stay was 1.7 days. For three patients, the PC was as judge as unresectable. A complete resection of the PC combined with HIPC was performed in seven out of the eight patients with PC considered resectable at laparoscopy. One patient was diagnosed with more extensive disease than that as assessed by the evaluative laparoscopy. Of note, for 20% of the patients with straight away laparotomy, the complete cytoreduction was not possible. CONCLUSION: Laparoscopic scoring of peritoneal carcinomatosis is accurate to assess the complete resectability of PC in patients for which there is inadequate or contradictory information concerning disease extent.

Thermal enhancement of oxaliplatin-induced inhibition of cell proliferation and cell cycle progression in human carcinoma cell lines.

Hyperthermia is used to treat intraperitoneal colorectal carcinomatosis. In this setting, the molecular effects of oxaliplatin and hyperthermia, in combination and alone, were deciphered in ovarian and colon cancer cells. The combined antiproliferative effects of hyperthermia and oxaliplatin (Eloxatine) on human IGROV-1 ovarian carcinoma, Caco-2 and HT-29 colon carcinoma cell lines were investigated by cell viability test, cell cycle analysis and modulation of expression of cell cycle-related proteins. Oxaliplatin inhibited growth of all cell lines in a dose-dependent manner. The efficacy of the drug was markedly enhanced by concurrent exposure to mild heat shock (1 h, 42 degree C). In IGROV-1 cells, a low concentration (15 microg/ml) of oxaliplatin in combination with hyperthermia induced a transient G2/M arrest. In both colon carcinoma cell lines, a G1/S arrest with a reduction of the G0/G1 population occurred. In IGROV-1 and Caco-2 cells, growth arrest was accompanied by apoptosis as suggested by the appearance of sub-G1 population. Time-course changes of cell cycle regulatory proteins levels revealed accumulation of cyclins A and B as well as of cdc2 and cdk2 upon exposure of IGROV-1 cells to hyperthermia and oxaliplatin. In this cell line, p53 appeared to be implicated in both G2/M arrest and apoptosis. G1/S arrest of HT-29 cells was linked to up-regulation of cyclin E and p27(Kip1) and accumulation of the hypophosphorylated form of pRB, whereas in Caco-2 cells only the hyperphosphorylated form was detected as well as a down-regulation of the proto-oncogene c-myc. Taken together, the results of these in vitro studies suggest that hyperthermia and oxaliplatin might elicit antiproliferative effects by modulating the expression of cell cycle regulatory proteins through different signalling pathways.