We analyzed expression of transforming growth factor (TGF)-alpha, epidermal growth factor (EGF) and their receptor, EGF receptor (EGFR), by immunohistochemistry in the human testis to determine the possible roles of these growth factors in human testicular function. Specimens were obtained from 17 patients including 9 patients with infertility, 4 patients with prostatic carcinoma and 4 patients with contralateral testicular tumor. EGF immunoreactivity was positive in the hyperplasic Leydig cells of one patient but negative in the other cases. On the other hand, strong TGF-alpha immunoreactivity was observed in Leydig cells, with weak staining in Sertoli cells and germ cells in cases with normal spermatogenesis. EGFR immunoreactivity was observed in the Leydig and peritubular cells, appearing as membrane staining. Marked immunoreactivity for TGF-alpha was observed in the Sertoli cells in testes with decreased spermatogenesis, especially in the Sertoli-cell-only syndrome. This finding may indicate a compensatory increase of TGF-alpha expression in the Sertoli cells accompanying a decrease in spermatogenesis. No significant correlation was found between the degrees of spermatogenesis and immunolocalization of the EGF receptor. These findings suggest that TGF-alpha is a locally produced growth factor that is involved in spermatogenesis in the human testis via an autocrine and/or paracrine mechanism.

In adrenal glands, oxidative free radicals are synthesized in the course of hormonal production, and enzyme superoxide dismutase (SOD) is considered to scavenge these harmful superoxide radicals and, subsequently, to protect the cells. We studied immunohistochemical localization of Mn (manganese)-SOD and Cu,Zn (copper-zinc)-SOD in human adrenal and its disorders from fetus to adult obtained from autopsy or surgery in order to examine the possible biological significance of these two enzymes. In fetal adrenal (n = 4), Cu,Zn-SOD and Mn-SOD were detected only in the fetal cortex. In adrenal glands from children (n = 21) to adults (n = 15), Mn-SOD immunoreactivity was exclusively detected in adrenal medulla, whereas Cu,Zn-SOD immunoreactivity was present only in adrenocortical parenchymal cells, weakly in the zona glomerulosa, and markedly in the zona reticularis. There were no differences in relative immunointensity and/or patterns of immunolocalization of these two SODs among different age groups. Both Cu,Zn-SOD and Mn-SOD immunoreactivity were detected in compact tumor cells of adrenocortical adenoma (n = 16). Marked immunoreactivity of both Cu,Zn-SOD and Mn-SOD was detected in adrenocortical carcinoma (n = 11) and pheochromocytoma (n = 5). These results indicate that Cu,Zn-SOD and Mu-SOD may play different roles as a scavenger or antioxidants in normal human adrenal glands, i.e., Cu,Zn-SOD as a scavenger of toxic superoxide radicals generated during steroidogenesis and Mn-SOD during catecholamine production. Cu,Zn-SOD and Mn-SOD immunoreactivities detected in adrenal neoplasms are also considered to represent altered expression of these enzymes associated with neoplastic transformation, as reported in other human malignancies.

Twenty-nine cases of bone metastases from renal cell carcinoma were examined. Eight had metastatic bone pain as the initial symptom and were diagnosed that the primary lesion was in a kidney. In eight cases bone metastases appeared after treatment of the primary site. Seven had only bone metastases and another 22 cases had multiple metastases in organs such as the lung and lymph node when the bone metastasis was found. Curable surgical treatment was performed in only 2 cases. The survival curve of these patients were: 1 year; 41 per cent, 2 year; 30 per cent and 3 year; 15 per cent. Bone scan used for detection of bone metastases of carcinoma frequently ends with false positive results. CT scan and angiography are available for differential diagnosis of bone metastasis. We examined 6 cases (9 lesions) of bone metastases from renal cell carcinoma (3 pelvic bones, 2 lumbar bones, 2 femurs and 2 humerus). All lesions were hypervascular by angiography and were easily diagnosed as bone metastases. For early detection of bone metastases from renal cell carcinoma, angiography is useful because hypervascularity and tumor stain are easily detected even in such small lesions as 2 cm. Angiography was also useful for chemoembolization.

We evaluated spermatogenesis in 36 patients with germ cell tumors [11 with seminoma (S) and 25 with nonseminoma (NS)] in terms of sperm concentration and histological score (Johnsen's mean score) of spermatogenesis in the ipsilateral and contralateral testes. We also measured the steroid concentration in the spermatic vein of the tumor-bearing side and performed biochemical and immunohistochemical studies of aromatase activity of the tumor to investigate the mechanism of exocrine and endocrine testicular dysfunction, with particular emphasis on the role of estrogen metabolism. The sperm concentration was significantly lower in patients with S (42.9 +/- 40.7 x 10(8)/mL) and NS (17.6 +/- 20.8 x 10(6)/mL) compared to normal adult men (114.4 +/- 41.2 x 10(6) mL; P < 0.01). The histological score was lower in patients with NS than in patients with S. The histological score was highest in the contralateral testis, followed by the ipsilateral testis far from the tumor and the ipsilateral testis near the tumor in both the S and NS groups. Serum levels of estradiol and hCG were significantly elevated in both the systemic and spermatic veins of patients with NS compared to normal values, but they were within normal limits in patients with S. The histological score count in the contralateral testis was significantly and inversely correlated with the tumor weight and serum levels of hCG and estradiol. Aromatase activity examined in 9 tumors (5 S and 4 NS) and 6 ipsilateral nonneoplastic testis (3 S and 3 NS) was significantly higher in both neoplastic and nonneoplastic testes in NS patients (tumor, 5.343 +/- 4.027; nontumor, 14.647 +/- 7.688 pmol/h.pg protein) compared to S patients (tumor, 0.622 +/- 0.408; nontumor, 1.979 +/- 1.164 pmol/h.pg protein). Aromatase immunoreactivity was observed in Leydig cells of the nonneoplastic testis in both S and NS patients and in interstitial or stromal cells in 16 of 25 of NS patients and none of S patients. Our results suggest that impaired spermatogenesis in patients with testicular germ cell tumor is caused by increased tumor size in both NS and S patients and/or by increased aromatization and in situ estrogen production in Leydig cells of the nonneoplastic testis and in interstitial or stromal cells of the tumor in patients with NS.

The most important information for treatment of bladder cancer is to know its exact staging. A whole layer needle biopsy technique has been developed for this purpose. Recently, neoadjuvant therapy has been used for invasive bladder cancer. Although down staging of bladder cancer after neoadjuvant therapy are evaluated by CT or ultrasound, these imaging are not reliable. We examined 11 invasive bladder cancer patients by whole layer needle biopsy pre and post neoadjuvant therapy. All cases were pT3-4 by pretreatment biopsy. After neoadjuvant therapy 4 were changed to pT0 by needle biopsy, other cases were no change or minimal change. In 4 changed to pT0, 3 were done total or partial cyctectomy and the results of pathological diagnosis of cystectomized specimens were also pT0. Another one case changed to pT0 is selected as candidate for bladder sparing and the patient is now in close surveillance. All 4 cases changed to pT0 were done combined treatment by chemo (internal iliac artery infusion) and radiotherapy. In remaining 7 cases, pathological staging of surgical or autopsy specimen agreed with that of whole layer needle biopsy. Whole layer needle biopsy showed no severe complication, except minor bleeding from the bladder wall. Tumor seeding into the needle tract was not observed up to present time. In conclusion, this biopsy system is useful for evaluation of the change of stage with chemotherapy and/or radiation therapy. By using this technique we can select the cases for candidate of bladder sparing.