No abstract

The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosomal alterations akin to leiomyoma and a malignant group with high chromosomal instability akin to leiomyosarcoma. Array-CGH genomic profile analysis was conducted for a series of 29 cases of uterine STUMP. A group of ten uterine leiomyomas and ten uterine leiomyosarcomas served as controls. The mean age was 50 years (range, 24-85) and the follow-up ranged from 12 to 156 months (average 70 months). Since STUMP is a heterogenous group of tumors with genomic profiles that can harbor few to many chromosomal alterations, we compared genomic indices in leiomyomas and leiomyosarcomas and set a genomic index ¼ 10 threshold. Tumors with a genomic index o10 were classified as nonrecurring STUMPs and those with a genomic index 410 represented STUMPs with recurrences and unfavorable outcomes. Hence, the genomic index threshold splits the STUMP category into two groups of tumors with different outcomes: a group comparable to leiomyomas and another similar to leiomyosarcomas, but more indolent. In our STUMP series, genomic analysis by array-CGH is an innovative diagnostic tool for problematic smooth muscle uterine lesions, complementary to the morphological evaluation approach. We provide an improved classification method for distinguishing truly malignant tumors from benign lesions within the category of STUMP, especially those with equivocal morphological features.

Melanoma is the most frequent solid tumor associated with leptomeningeal metastasis (LM). The usual diagnostic tools, that is, cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium-enhanced MRI of the entire neuraxis both lack effectiveness. The CellSearch Veridex technology for the detection of circulating tumor cells (CTC) in blood was designed for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer, which express EpCAM markers. We have previously adapted this technology to detect malignant cells in the CSF of breast cancer LM. Our objective here was to check if this technology would also allow the detection and the enumeration of CTC in the CSF of melanoma patients presenting with LM although melanoma does not express EpCAM markers. On the occasion of the intrathecal treatment of LM in 2 melanoma patients, 5 mL of CSF and 7.5 mL of blood were collected on CellSave Preservative Tubes and analyzed within 3 days after CSF sampling using a melanoma-dedicated kit. The CellSearch Veridex technology was then adapted to direct enrichment, enumeration, and visualization of melanoma cells in the CSF. CD146+, HMW-MAA+, CD34-, and CD45- cells with typical morphology could be observed and enumerated sequentially with reproducible results, corresponding to CSF melanoma cells (CSFMC). In contrast to the current gold standard cytomorphological analysis, this new approach allowed a precise quantification of CSFMC in all samples concomitantly analyzed. This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of melanoma patients with LM.

Ovarian cancer (OVC) is the fourth leading cause of cancer mortality among women in Europe and the United States. Its early detection is difficult due to the lack of specificity of clinical symptoms. Unfortunately, late diagnosis is a major contributor to the poor survival rates for OVC, which can be attributed to the lack of specific sets of markers. Aside from patients sharing a strong family history of ovarian and breast cancer, including the BRCA1 and BRCA2 tumor suppressor genes mutations, the most used biomarker is the Cancer-antigen 125 (CA-125). CA-125 has a sensitivity of 80 % and a specificity of 97 % in epithelial cancer (stage III or IV). However, its sensitivity is 30 % in stage I cancer, as its increase is linked to several physiological phenomena and benign situations. CA-125 is particularly useful for at-risk population diagnosis and to assess response to treatment. It is clear that alone, CA-125 is inadequate as a biomarker for OVC diagnosis. There is an unmet need to identify additional biomarkers. Novel and more sensitive proteomic strategies such as MALDI mass spectrometry imaging studies are well suited to identify better markers for both diagnosis and prognosis. In the present review, we will focus on such proteomic strategies in regards to OVC signaling pathways, OVC development and escape from the immune response.