Xavier Leroy

Leroy X, Aubert S, Zini L, Franquet H, Kervoaze G, Villers A, Delehedde M, Copin M‐C & Lassalle P (2010) Histopathology56, 180–187 Vascular endocan (ESM‐1) is markedly overexpressed in clear cell renal cell carcinoma Aims:  In kidney cancer, new anti‐angiogenic therapies have emerged requiring parameters of effectiveness. The aim was to analyse the expression of endocan or endothelial cell‐specific molecule‐1, which is a proteoglycan up‐regulated in presence of pro‐angiogenic factors.Method and results:  We investigated 44 renal clear cell carcinomas (RCC) and 25 papillary carcinomas (PC). Circulating endocan was detected by enzyme‐linked immunosorbent assays (ELISA) in 14 patients with RCC, in eight with PC and in 15 healthy volunteers. Endocan was detected by immunohistochemistry in endothelial cells in almost all the cases of RCC without immunoreactivity in tumour cells. In PC, only 5/25 tumours exhibited weak immunoreactivity. Reverse transcriptase‐polymerase chain reaction study confirmed that endocan levels were strongly increased in RCC. Endocan was also detected by ELISA at levels from 3‐ to 10‐fold higher in the sera of patients with RCC. In vitro, addition of sunitinib prevented the release of endocan in human umbilical vascular endothelial cells when induced by vascular endothelial growth factor.Conclusions:  Our results showed that endocan is overexpressed in patients with RCC. Endocan could therefore appear as a marker of interest in the follow‐up and may be a potential parameter to monitor the tumour response to anti‐angiogenic therapeutics.

To define specific staining patterns for the adhesion/growth-regulatory lectin tandem-repeat-type galectin-8 in hypopharyngeal and laryngeal tumor progression and relate these parameters to galectins 1, 3 and 7 in the quest to explore the galectin network. The level of expression of galectin-8 was determined immunohistochemically in a series of 18 and 16 cases of tumor-free epithelium, 24 and 10 cases of low-grade dysplasia, 22 and 15 cases of high-grade dysplasia located in peri-tumoral area of 74 and 37 hypopharyngeal and laryngeal carcinomas. Marked upregulation in galectin-8 staining intensity and immunopositive area in malignancy versus dysplasia was seen in hypopharyngeal cancer (p<10(-6)), in laryngeal cancer for labeling index and high-grade dysplasia/carcinoma (p<10(-6)). No correlation to recurrence was delineated. The presented data revealed a divergence within the galectin-1, -3, -7 and -8 network during tumor progression.

Galectin-1 has been found to modulate lymphocyte invasion in inflammation and to be involved in angiogenesis in models, thus prompting examination of its clinical relevance in laryngeal cancer. Immunohistochemical processing of tissue sections (n=53) from patients with stage I/II (n=35) and stage IV (n=18) laryngeal squamous cell carcinoma (LSCC) with a specific anti-galectin-1 antibody and monitoring of CD45/CD31 positivity was combined with quantitative morphometric analysis. Lectin presence in the tumor and endothelial cells was positively correlated, while a negative relationship to the number of CD45-positive lymphocytes was demonstrated. No association was seen with the extent of neovascularization. The mean optical density (MOD) of lectin-dependent staining in the tumor stroma was significantly increased compared to normal stroma. Galectin-1 was not associated with angiogenesis in the studied cohort while galectin-1 in endothelial cells may negatively influence lymphocyte invasion and the mean optical density for the stromal galectin-1 signal is up-regulated in tumors.

Context. —Adenocarcinomas of the sinonasal tract are classified into 4 categories: salivary-type, intestinal-type, nonintestinal-type, and metastatic. Signet-ring cell carcinoma is the rarest form of intestinal-type adenocarcinoma. Only isolated cases have been reported in the literature. Objective. —To evaluate clinical attributes, morphology, and immunohistochemistry in signet-ring cell carcinoma of the sinonasal tract. Design. —Seventy-three cases of primary sinonasal adenocarcinomas were retrieved from the files. Only 5 signet-ring cell adenocarcinomas (tumors composed of more than 90% signet-ring cells) were identified. In all cases, clinical data and histologic slides were available and were reviewed. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC2, MUC5AC, MUC5B, MUC6, p53 protein, and MIB-1. Results. —Four of our 5 patients were woodworkers. They were treated by surgical excision and radiotherapy. Patient follow-up ranged from 11 to 84 months. Three patients presented an unfavorable evolution and died of metastatic spread. Microscopically, the tumors produced abundant mucin deposits, which accumulated in large extracellular pools. Tumor cells were predominantly signet-ring cells floating in the pools of mucin. The mucins profile was MUC2 ⁺ , MUC5AC ⁺ , MUC5B ⁺ , and MUC6 ⁻ . Eighty percent of cells were immunostained by p53 protein antibody and 60% cells with MIB-1 antibody. Conclusions. —The mucin profile is similar to the profile described in digestive tract adenocarcinoma. It is not useful to differentiate between metastatic adenocarcinoma and primary intestinal-type sinonasal adenocarcinoma. Clinical data and immunochemistry with p53 protein and MIB-1 confirm that sinonasal signet-ring cell carcinoma is a high-grade and aggressive tumor.

Invasive urothelial carcinoma may present with many deceptive morphologic variants. We report the clinicopathologic and immunohistochemical features of 5 cases of the so-called lipid-cell variant of urothelial carcinoma. The tumors occurred in 4 men and 1 women aged from 56 to 80 years. Four cases were developed in the bladder and 1 case in the renal pelvis. All cases were revealed by a macroscopic hematuria. The tumors were composed of sheets and nests of large epithelial cells with an abundant clear multivacuolated cytoplasm mimicking lipoblasts. Nuclei were irregular, hyperchromatic, eccentric, and frequently indented by cytoplasmic vacuoles. Mucin stains (PAS, Alcian Blue) were negative. Tumor cells were strongly stained with cytokeratin 7, cytokeratin 20, and EMA but were negative with S-100 protein. In all cases, a usual high-grade urothelial carcinoma component was admixed with lipoid tumor cells. Two tumors infiltrated the bladder muscle, 2 cases invaded the bladder submucosa, and 1 case invaded the renal parenchyma. In the follow-up, despite appropriate surgical treatment, 4 patients died of the disease and 1 patient is alive without recurrence. Because of its rarity and the tumor cells' appearance, the lipoid-cell variant may be misdiagnosed and must be distinguished from liposarcoma or signet-ring cell carcinoma. In the present series, the lipoid-cell variant of urothelial carcinoma was associated with an aggressive behavior and a poor prognosis.