Masaharu Kan

High-level Expression of the CD44 Variant Sharing Exon v10 in Renal Cancer

To examine whether renal cell carcinoma displays altered CD44 expression we performed reverse transcription‐polymerase chain reaction (RT‐PCR) analysis of CD44 in 38 specimens from renal cancer, normal kidney and metastases of 19 patients and 6 renal cancer cell lines. To detect the CD44 variants, we utilized the RT‐PCR Southern blot method. One out of 19 (5.3%) renal cancer specimens expressed a larger molecular weight band than 1 kb by RT‐PCR analysis, in contrast to previous findings in colon and breast cancer. The band patterns in RT‐PCR were different in 14/17 (82.4%) cases between normal kidney and tumors, and a band of about 700 bp was especially marked in 12/17 (70.6%) tumor specimens and 4/6 (66.7%) cell lines. By cloning and sequencing of the 700 bp band, we found that this variant is identical to the CD44 variant sharing only exon v10. Examination by Northern blot analysis has revealed that all tumors express a higher level of CD44 mRNA than paired normal kidneys. These findings suggested that the CD44 variants sharing exon v10 play some role in renal cancer.

Frequency of Mutations of Insulin Receptor Gene in Japanese Patients With NIDDM

To examine the prevalence of abnormalities in the insulin receptor structure gene in Japanese Patients with non-insulin-dependent diabetes mellitus (NIDDM), a population of 51 patients with NIDDM was screened for mutations in this gene. Patient genomic DNAs of both alleles corresponding to 22 exons of the gene were amplified by polymerase chain reaction (PCR). The PCR products on pUC19 were sequenced. Three patients with heterozygous missense mutation Thr831→Ala831 in exon 13 and one patient with heterozygous missense mutation Tyr1334→Cys1334 in exon 22 of the ²-subunits were identified. Linkage analysis of one of the families plus statistical studies showed that the mutation Thr831→Ala831 is possibly responsible for the onset of NIDDM. In COS cells transiently expressing both mutant receptor cDNAs and a cDNA of a Mr 85,000 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase), the mutation Tyr1334→Cys1334 impaired binding of the receptor with the Mr 85,000 subunit of PI 3-kinase, but linkage analysis of the family showed that the mutation did not cosegregate with NIDDM in the pedigree. Therefore, one missense mutation (Thr831→Ala831) in the insulin receptor, as found in three patients, is possibly involved in the etiology of a subset of the 51 NIDDM patients.

Serological evaluation of soluble CD44 in renal cancer

In this study, we examined the feasibility of using elevated serum CD44 concentration as an indicator in renal cancer. We performed enzyme‐linked immunosorbent assays using 63 sera obtained from 47 patients with renal cancer and 16 healthy controls and evaluated the clinico‐pathological parameters. The concentration of soluble CD44 standard (sCD44std), indicating the concentration of all circulating CD44 isoforms, was significantly higher in renal cancer patients than in normal individuals (745±170 ng/ml vs. 563±159 ng/ml, P=0.001). The concentration of soluble CD44 splice isoforms sharing exon v6 (sCD44v6) was also higher in the same patients (287±121 vs. 220±59, P=0.056). However, there were no correlations between the concentrations of sCD44std or sCD44v6 and clinico‐pathological parameters such as grade, stage, histological type, tumor size and growth type. The ratio of sCD44std/sCD44v6 was higher in the rapid growth‐type cancers than in the slow growth‐type cancers (3.95±2.12 vs. 2.63±0.82, P=0.014). These findings suggested that the serum concentration of unknown soluble CD44 isoforms not sharing exon v6, which are present in sCD44std, increases in patients with rapid growth‐type cancers. These findings indicated that sCD44std and sCD44v6 are not useful indicators of tumor burden and metastasis in patients with renal cancer, but that an unknown sCD44 isoform(s) plays a role in the biological behavior of the rapid growth‐type cancers.

A case of renal cell carcinoma producing granulocyte-macrophage colony-stimulating factor.

Renal cell carcinomas frequently secrete hormones and cytokines (parathormone, prostaglandins. renin, gonadotropins and glucocorticoids). The underlying cause of the leukemoid reaction sometime seen in renal cell carcinoma is unknown. We report a case of renal cell carcinoma with leukemoid reaction and demonstrate that the autonomous production of granulocytemacrophage colony-stimulating factor in cancer tissue was the underlying mechanism.

MP97-03 APPLICATION OF LOCAL 18F-FLUORO-2-DEOXYGLUCOSE UPTAKE BY THE PROSTATE TO ASSESS PERIOPERATIVE RESULTS OF ROBOT-ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY.

INTRODUCTION AND OBJECTIVES: Little glucose metabolism is generally thought to occur in prostate cancer, leading to low diagnostic accuracy of 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT). Nevertheless, this modality is reportedly useful for identifying high-risk local cancers. We therefore investigated whether local FDG uptake by the prostate reflects the perioperative results of robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: Between November 2012 and August 2016, a total of 248 patients underwent RALP at our institution. Of these, subjects in this study comprised 116 patients in whom FDG-PET/CT was employed for preoperative staging. We retrospectively compared perioperative results between patients, stratified for local FDG uptake in the prostate. Patients who had received preoperative hormone therapy were excluded from the study. FDG uptake was rated based on clinical reports prepared by two radiation diagnosticians. Patient background characteristics, perioperative results and postoperative pathological results were compared between subjects divided into PET-positive and -negative groups. RESULTS: Participants comprised 40 PET-positive subjects and 76 PET-negative subjects. Among the patient background characteristics, mean age was slightly but significantly higher in the PETpositive group (66 years) than in the PET-negative group (64 years; p1⁄40.0485). No significant differences were seen in PSA level, clinical T stage or Gleason Score (GS). Operative time, console time and volume of blood loss also showed no differences between groups, and no patients in either group suffered rectal perforation or required blood transfusion. Postoperative urethral balloon retention time and urinary continence rate at 3 months postoperatively were comparable between groups. Postoperative pathological results showed significantly higher values for the following parameters in the PET-positive group than in the PET-negative group: extraprostatic invasion (45.0% vs 22.4%; p1⁄40.0185); positive margin (30.0% vs 13.2%; p1⁄40.0445); and GS 1⁄48 (52.5% vs 23.7%; p1⁄40.00343). Multivariate analysis also showed that PET positivity tended to be associated with positive margins (odds ratio (OR), 2.45; p1⁄40.0819) and extraprostatic invasion (OR, 2.34; p1⁄40.0529), while GS 1⁄48 was a significant predictor (OR, 3.08; p1⁄40.0208). CONCLUSIONS: In RALP, FDG uptake should be considered a predictor of high-grade disease and a risk factor for positive margins.

FEMALE PARAURETHRAL LEIOMYOSARCOMA: A CASE REPORT

A 54-year-old woman visited another hospital with complaining of a palpable mass in vagina and dysuria. The mass had gradually enlarged since the past 2 years. Ultrasonography and CT revealed the tumor located between the urethra and vaginal mucosa. Histopathological examination was well-differentiated leiomyosarcoma from transvaginal needle biopsy. She was referred to our hospital. On MRI, the 4-cm tumor showed no infiltration into the vaginal mucosa or urethra. PET/CT showed a high uptake of FDG. No metastatic disease was evident. We performed excision of the tumor transvaginally. The tumor cells demonstrated immunoreactivity for estrogen receptors and partially progesterone receptors in histopathological examination. We speculated that the developmental mechanism of female paraurethral leiomyosarcoma was associated with female leiomyosarcoma in other surrounding pelvic organs.