Immunohistochemical findings of nitric oxide synthase expression in urothelial transitional cell carcinoma including dysplasia.

Several in vitro studies have shown that nitric oxide (NO) produced by NO synthase (NOS), such as inducible NOS (iNOS) play an important role in tumor biology. We immunohistochemically examined the expression of iNOS and p53 proteins in patients with transitional cell carcinoma (TCC) of the urinary tract, including adjacent dysplastic lesions to determine the significance of the tumor behavior. Of total 94 tumors, in the present study, 41 (43.6%) tumors exhibited homogeneous immunostaining (diffuse strong positivity in tumor cells, >60%) and 53 (56.4%) tumors heterogeneous staining (variable positivity in tumor cells, 20-60%). No TCCs exhibited negative iNOS immunostaining was found. Thirty (31.9%) of 94 TCCs were positive with anti-p53 antibody, including 23 of homogeneous and 7 of heterogeneous staining. Of 23 TCCs with homogeneous p53 immunostaining, 11 tumors exhibited homogeneous iNOS immunoreaction. In the present study, dysplastic lesions adjacent to carcinomas were detected in 64 cases including 36 TCCs with homogeneous iNOS expression. All dysplastic lesions adjacent to the 36 TCCs with homogeneous iNOS immunostaining exhibited homogeneous iNOS immunostaining. No significant association between iNOS immunoreactivity and any clinicopathological factors as well as p53 immuno-reactivity were found. These in vivo findings provide evidence for frequent iNOS protein expression in TCC. In addition, our observations indicate that overexpression of iNOS expression may be one of the early events in the carcinogenesis of TCC.

Determination of p53 protein and high-risk human papillomavirus DNA in carcinomas of the renal pelvis and ureter.

The presence and distribution of high-risk human papillomavirus (HPV) DNA type-16 and -18 or overexpression of the p53 protein were determined in 31 patients with renal pelvic and ureteral carcinoma in Saga prefecture of Japan, consisting of 28 transitional cell carcinomas (TCCs) and 3 squamous cell carcinomas (SCCs). In situ hybridization with DNA probes for HPV-16 and -18 was performed as well as immunohistochemical techniques using antibody to p53 protein. Fresh tumor tissues from 8 patients were also studied for p53 mutations in exons 5 through 8 by direct sequencing. Of 28 TCC patients at Saga prefecture in Japan, 10 tested were positive for HPV DNA, 5 for HPV type-16, 4 for HPV type-18 and one doubly-positive case. Of the remaining 18 tumors, seven showed positive nuclear staining in cancer cells with p53 antibody. One of the 3 patients with SCCs also revealed the nuclear positivity of the cancer cells with p53 antibody but not with HPV infection. p53 point mutation was detected in 2 cases also showing p53 immunopositivity. Overexpressed p53 protein was statistically more common in invasive and non-papillary (p<0.05) and in high-grade TCCs (p<0.05). These findings suggest that HPV infection, and expression (mutation) of p53 protein may be intimately related to the pathogenesis of urothelial tumor cell growth and progression.

Overexpressed cyclin D1 protein related to p53 and retinoblastoma proteins in transitional cell carcinoma of the urinary tract.

We employed immunohistochemical methods to investigate the overexpression of cyclin D1 protein as well as p53 protein and retinoblastoma protein (pRb) in 57 patients with transitional cell carcinoma (TCC) of the urinary tract, in order to determine their frequency and significance, and also association with the clinicopathological behavior of this tumor. Nuclear immunostaining with cyclin D1 antibody revealed 7 homogeneously stained tumors (12.3%), including 4 heterogeneous pRb expressions, of which only one was also positive for p53. Positive immunostaining with each antibody to p53 or pRb was obtained in 15 (26.3%) and 49 (86%) tumors, respectively. The 49 pRb-positive tumors included 6 homogeneous and 43 heterogeneous nuclear immunostaining patterns. The remaining pRb-negative 8 tumors included 5 cyclin D1-negative tumors. The prevalence of p53 staining was higher in high-grade (P<0.05) and invasive types of tumors (P<0.05) than the other types studied. On the other hand, no significant relationship was found between cyclin D1- or pRb-immunoreactivity and clinicopathological factors. These findings provide evidence for infrequent cyclin D1 protein overexpression in TCC independently associated with p53 protein and/or pRb overexpression.

Granular cell tumor expressing myogenic markers in the prostate.

A granular cell tumor in the prostate of a 72 year old male is reported. The tumor nest was composed of large polygonal tumor cells, possessing cytoplasmic eosinophilic granules which were positive with PAS stain and resistant to diastase digestion. Immunohistochemically, most tumor cells were strongly positive with anti-alpha-smooth muscle actin and -neuron specific enolase antibodies. Only a few scattered tumor cells were reacted with anti-S-100 protein antibody. These findings might suggest smooth muscle differentiation of this case, and provide an additional insight into the histogenesis of granular cell tumors, especially in their heterogeneity.

Detection of p53 and bcl-2 protein in carcinoma of the renal pelvis and ureter including dysplasia.

Ninety-four patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter, including dysplastic lesions, were studied for p53 and bcl-2 protein expression by immunohistochemistry. Twenty-one patients were also studied for p53 gene mutations by direct sequencing and for bcl-2 gene rearrangement by Southern blot analysis. Overexpressed p53 protein was detected in 26 cases (27.7 per cent). bcl-2 immunostaining was observed in 21 tumours (22.3 per cent), including four cases with labelling for p53. Furthermore, the dysplastic lesions surrounding 19 p53-positive tumours also stained for p53. bcl-2 expression was also detected frequently in dysplastic lesions adjacent to 14 bcl-2-positive TCCs. Positive reactions of dysplastic lesions were also found adjacent to 37 bcl-2-negative tumours. p53 point mutation was detected in 6 of 21 cases. Five of the six cases were positive for p53 protein. blc-2 positivity was detected in 3 of 21 tumours, without bcl-2 gene rearrangements in the major breakpoint region. Overexpressed p53 protein was frequently detected in both high-grade (P < 0.05) and invasive tumours (P < 0.05). In three cases of p53-positive non-papillary invasive tumours, bcl-2 was found in non-invasive portions, but was not present in invasive areas. These findings suggest that overexpression (mutation) of p53 and/or bcl-2 protein may be early events in tumourigenesis and that p53 alterations in particular are essential for the maintenance of a malignant phenotype in tumour development.

p53 and human papillomavirus DNA in renal pelvic and ureteral carcinoma including dysplastic lesions.

Ninety-eight cases of transitional-cell carcinoma (TCC) of the renal pelvis and ureter, including dysplastic lesions, were studied for tumor incorporation of human papillomavirus (HPV) type-16 and type-18 DNA by in situ hybridization (ISH) with DNA probes for each HPV viral type. Immunohistochemical analysis of p53 expression was also performed. Fresh tumor tissues from 26 patients were also studied for p53 mutations in exons 4 through 9 by direct sequencing and for HPV infection by polymerase chain reaction (PCR). Thirty-two tumors were positive for HPV DNAs, including 6 double-positive cases. Among these tumors, adjacent dysplastic lesions in 21 cases (66%) also revealed identical reactivity. Overexpressed p53 was detected in 26 cases. Expression of p53 was also detected in dysplastic lesions in 19 out of these 26 cases (73%). Three cases were positive for both HPV DNA and p53 antibody. p53 point mutation was detected in 7 of 26 cases, 6 of which were also positive for p53. HPV type-16 DNA was detected in 6 cases by PCR, 4 of which were also ISH-positive. Overexpressed p53 was frequently detected in invasive and non-papillary tumors (p < 0.01) and in high-grade tumors (p < 0.05). HPV infection was more common in non-invasive and papillary tumors (p < 0.05). These findings suggest that HPV infection or overexpression (mutation) of p53 may be an early event and be related to phenotypes of tumor-cell growth patterns and progression.

[Value of PSA/gamma-Sm ratio (P/S ratio) for diagnosis of prostate cancer in patients with urinary retention].

It is known that serum prostate specific antigen (PSA) in urinary retention due to benign prostatic hypertrophy (BPH) increase. To evaluate prognostic value of the ratio of serum PSA to gamma-seminoprotein (P/S Ratio) for prostate cancer (PC) in patients with urinary retention, we have studied the P/S Ratio at the initial examination in 33 patients with untreated PC (10 with and 23 without urinary retention) and 193 patients with untreated BPH (38 with and 155 without urinary retention) histopathologically diagnosed at our hospital between January, 1992 and December, 1993. The results were as follows: 1) The mean P/S ratio of PC patients was significantly higher than that of BPH patients in both groups with and without urinary retention. 2) When the cut off value of P/S Ratio was determined to be 1.35, the highest efficiency, 59.3% was obtained in the group without urinary retention. The sensitivity and specificity were 65.2% and 91.0%. 3) In the group with urinary retention, the efficiency was also the highest, 80.0% with a cut off value of 1.35. The sensitivity and specificity were 80.0% and 100%. 4) In all patients, the efficiency was 64.6%, the sensitivity was 69.7%, and the specificity was 92.7% with a cut off value of 1.35. 5) Positive rate of serum PSA in BPH patients with urinary retention was 47.4% and that in BPH patients without urinary retention was 17.4%. The mean P/S ratio of the BPH patients with urinary retention was significantly lower than that of BPH patients without urinary retention, which suggested that the serum free PSA increase in the former.(ABSTRACT TRUNCATED AT 250 WORDS)

[Nephrogenic adenoma of the ureter: a case report].

A 27-year-old male with nephrogenic adenoma of the ureter complicating urolithiasis is reported. Nephrogenic adenoma of the ureter is extremely rare, and this case is the sixth reported in Japan. The lesion was found at the site of the stone in the left ureter. Histopathologically, the tumor consisted of ducts resembling uriniferous tubules, and no signs of malignancy were noted. The cause of nephrogenic adenoma is considered to be metaplastic reaction to stimulation by stones and inflammation.

[Thromboangiitis obliterans of the spermatic cord: a case report].

A 61-year-old man was admitted to our hospital with a 8-day history of dull pain and swelling in the bilateral scrotum and bilateral inguinal region. Neoplasma of the spermatic cord was suspected, and bilateral orchiectomy was immediately carried out. Histopathological examination revealed thromboangiitis obliterans of the spermatic cord. The differential diagnosis of a tumorous lesion in the inguinal region is frequently difficult. In such a case, surgical exploration is recommended, and a biopsy must be performed for a definitive diagnosis, but orchiectomy should not be readily selected. Our patient is the first reported case in Japan to our knowledge.

[Two cases of urinary tract abnormalities (ectopic ureterocele and VUR) associated with complete duplex kidney].

Two patients with complete duplex kidney accompanied by ectopic ureterocele and vesicoureteral reflux (VUR) had repeated episodes of refractory urinary tract infection. One patient was a 11-year-old girl who showed VUR into the cele ureter. The other patient was a 17-year-old female who showed VUR into the mate ureter. Satisfactory results could be obtained by twin ureteroneocystomy with cele wall resection in both cases. Complete duplex kidney is often complicated by urinary tract abnormalities such as ectopic ureterocele, VUR, and renal dysplasia, and these complications complicate its diagnosis. The treatment of complete duplex kidney with urinary tract abnormalities are discussed.

[Primary squamous cell carcinoma of the prostate: a case report].

Primary squamous cell carcinoma of the prostate is so rare that only 6 cases have been reported in the Japanese literature. This type of cancer is independent of androgen, and its prognosis seems to be generally poor. The patient was a 76-year-old male who was admitted to our hospital with a chief complaint of dysuria. Although the markers for prostatic tumor were within normal ranges, findings in digital examination and imaging suggested prostatic cancer. Because of the marked dysuria, transurethral resection of prostate serving as a biopsy was carried out, and histopathological examination led to a diagnosis of squamous cell carcinoma. Despite 2 courses of chemotherapy with pepleomycin and cis-platinum (CDDP), followed by radiotherapy, the patient died from cancerous cachexia about 9 months after the initial examination.