To clarify whether germ cell apoptosis is related to a decrease of germ cells in the aged testis with impaired spermatogenesis, we investigated the apoptotic rate of each germ cell type. Testicular specimens were obtained by orchiectomy from 36 men with advanced prostate cancer and by testicular biopsy from 21 men with obstructive azoospermia, which served as controls. The terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) technique was used to identify apoptosis. As a marker of cell proliferation activity, the expression of Ki-67 was immunohistochemically evaluated. Expression of Bcl-xl, which regulates apoptosis of germ cells, was also immunohistochemically examined. Histologically, except for spermatogonia, the ratios of primary spermatocytes, round spermatids, and elongated spermatids to Sertoli cells were significantly decreased in aged testes. The apoptotic rate in spermatogonia was significantly lower in aged men than it was in controls (0.11% +/- 0.06% vs 0.34% +/- 0.21%). Expression of Ki-67 in spermatogonia was decreased in aged men (18.6% +/- 6.0%) compared with that of controls (24.9% +/- 3.3%), suggesting that germ cell proliferation diminished with aging. Consequently, the balance of spermatogonial proliferation and apoptosis showed no difference between the two groups. This was believed to be one of reasons why spermatogonial numbers in aged testes was similar to those of controls. The apoptotic rate of primary spermatocytes in aged men was significantly elevated compared with that of controls (0.60% +/- 0.54% vs 0.22% +/-0.12%), resulting in a decrease of the number of primary spermatocytes per Sertoli cell. The expression of Bcl-xl was inversely correlated with the apoptotic rate in primary spermatocytes, suggesting that Bcl-xl may be related to the regulation of primary spermatocyte apoptosis. Based on these findings, we conclude that accelerated apoptosis of primary spermatocytes might account for a part of the mechanism of germ cell loss in aging men.

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We found a significant correlation between lung cancer in smokers and the expression of a human gene, D40, predominantly expressed in testis and cancers. In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40. A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14. D40 mRNA is predominantly expressed in normal testis tissue. However, this gene is also expressed in various human tumour cell lines and primary tumours derived from various organs and tissues, such as lung cancer. We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer. D40 expression did not significantly correlate with either histological type or pathological tumour stage. However, D40 expression was observed more frequently in poorly differentiated tumours than in well or moderately differentiated ones. Furthermore, the incidence of D40 expression was significantly higher in tumours from patients who smoke than in those from non-smokers. D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients.

The present study revealed significant differences in the results of estimation of testicular volume among the ten investigators, but intra-investigator variation was not considerable. Improved training and proper standardization of the measurement will be necessary before starting a multi-center study based on an andrological examination.

We have previously identified and cloned a human gene, D40, that is preferentially expressed in testis among normal organs, while it is widely expressed in various human tumor cell lines and primary tumors derived from different organs. In this report, we have examined the expression and localization of this protein in human testis with an antibody specific to D40 protein. In Western analyses, the anti-D40 antibody recognized a major band with a molecular mass of 300 kDa and a minor band of 250 kDa. These bands were not observed in the testis lysates from patients with Sertoli-cell-only syndrome and with Kleinfelter syndrome, who lack germ cells of the testis, indicating that D40 protein is expressed in the germ cells of normal testis. Immunohistochemical studies have revealed that D40 protein is highly expressed in spermatocytes and in the pre-acrosome of round spermatids. In the acrosome, D40 protein expression is observed not inside but outside the acrosome membrane. This is consistent with the finding that the amino-acid sequence at the amino terminal of the D40 protein lacks a hydrophobic signal peptide that is required for proteins to translocate to the membrane. Expression of D40 protein is observed in the acrosome of ejaculated spermatozoa as well, although the level is low compared with that in the pre-acrosome of spermatids. These results suggest that D40 protein plays important roles in spermatogenesis, especially in the formation and maintenance of the acrosome.

We present a case of squamous cell carcinoma of the testis that metastasized from lung cancer. The patient, who had received left pneumonectomy 2 years earlier for squamous cell carcinoma (SCC) of the lung, developed pulmonary metastasis, which was treated with chemotherapy. Although the recurrence regressed after treatment, the testicular tumor progressed gradually. Left radical orchiectomy was performed. Pathological examination revealed metastatic SCC. Testicular metastasis from lung cancer is a very rare disease.

Objective: To review clinical outcome of patients with adrenocortical carcinoma experienced at a single institute over 34 years. Methods: The study included 14 patients who were diagnosed as having the disease and were treated at the Department of Urology, Sapporo Medical University Hospital between 1973 and 2006. Their clinical features and outcomes were reviewed. Results: Of the 14 patients, there were nine men and five women. The median follow-up period was 13.0 months (range, 1-213). Two patients were classified as having stage II disease, seven as stage III and five as stage IV. The disease was completely removed in eight patients and incompletely in three. Two other patients received exploratory laparotomy only. The remaining one patient had no indication for surgery. The median survival periods were 2 months in patients with stage IV and 108 months in those with stages II and III (P = 0.136). Mitotane treatment in the adjuvant setting did not clearly affect the clinical courses of patients without metastasis. However, the treatment was effective for metastasis that was repeatedly developed as late recurrence in one patient. Three patients with metastasis at diagnosis received combination chemotherapy with etoposide, doxorubicin and cisplatin (EDP) with or without mitotane treatment, to which lung metastasis completely responded in one patient. Conclusions: Adrenocortical carcinoma is a rare disease but frequently recurs. The best chance of survival may be achieved by early detection and complete surgical removal. There may be patients who possibly benefit from mitotane treatment with or without EDP, although this remains to be conclusively determined.

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