Haptoglobin-beta chain defined by monoclonal antibody RM2 as a novel serum marker for prostate cancer.

In our previous study, monoclonal antibody RM2, established toward the glycosyl epitope, reflected grade of malignancy of prostate cancer cells whereas RM2 reactivity to benign glands was negative or weak. RM2 reactivity was also detected in stroma, suggesting the glycoprotein RM2 recognizes could be released into the bloodstream. Then, we explored RM2 reactivity to sera of early prostate cancer. We compared RM2 reactivity to sera between 62 patients with early prostate cancer and 43 subjects with benign prostatic disease, and examined RM2 reactivity before and after radical prostatectomy in 15 patients by Western blotting. We also examined RM2 reactivity to sera of the other urogenital cancers. RM2 reactivity was significantly enhanced on a serum glycoprotein with molecular mass approximately 40 kDa, hereby termed GPX, in the patients with early prostate cancer when compared with those with benign prostatic disease (p < 0.0001). Setting an appropriate cutoff level, RM2 reactivity to GPX for detection of prostate cancer had sensitivity of 87% and specificity of 84%, respectively. Furthermore, the level of RM2 reactivity significantly decreased after radical prostatectomy (p = 0.006). However, increased RM2 reactivity to GPX was also observed in the other urogenital cancers. The proteomics approach identified GPX as haptoglobin-beta chain and RM2 showed preferential reactivity toward haptoglobin-beta chain derived from prostate cancer when compared with polyclonal anti-haptoglobin antibody. Haptoglobin-beta chain defined by RM2 is a novel serum marker that may be useful for detection of early prostate cancer when coupled with prostate-specific antigen because it is not specific to prostate cancer.

Morphological subtyping of papillary renal cell carcinoma: clinicopathological characteristics and prognosis.

AIM: The aim of the study was to evaluate the clinicopathological and prognostic significance of morphological subtyping of papillary renal cell carcinoma (PRCC). METHODS: The patients treated for renal cell carcinoma in our department from January 1985 to March 2006 were evaluated retrospectively. Thirty-two of the 591 patients (5.4%) were diagnosed with PRCC. To determine the prognostic factors, we re-evaluated the pathological stage according to the 2002 TNM classification of malignant tumors, and the tumor type of renal cell carcinoma according to the 2004 World Health Organization histological classification. Survival was analysed using the Kaplan-Meier method and the log-rank test. RESULTS: The age at diagnosis ranged from 33 to 81 years (median: 63 years old) and the follow-up time after the surgical treatment ranged from 4 to 191 months (median: 54 months). The cancer-specific 5-year survival rate of the 32 PRCC patients was 74%. Pathologically, 17 patients (53%) and 15 patients (47%) were diagnosed with type 1 and type 2 PRCC, respectively. The type 2 PRCC patients had a significantly higher tumor grade (P < 0.001), a more advanced stage (P < 0.001), more frequent vascular invasion (P < 0.001), and a higher sarcomatoid component (P = 0.038) compared to the type 1 PRCC patients. The type 1 patients had a better cancer-specific 5-year survival rate than the type 2 patients (94% vs 50%) (P = 0.008). CONCLUSION: The morphological subtyping of PRCC is significantly associated with clinicopathological features and the prognosis. Our results provide evidence of the clinical utility of dividing PRCC into two subtypes.

Intravenous extended liposarcoma arising from renal sinus.

Liposarcoma arising from the renal sinus is rare and there have been no reports of intravenous extended liposarcoma of the renal sinus thus far. We report a case of liposarcoma of the renal sinus that extended into the renal venous lumen. A 58-year-old woman was referred to our hospital for an intravascular fatty tumor of the right renal vein incidentally discovered by an abdominal screening ultrasonogram. Computer tomography revealed a fatty tumor extending from the right kidney to the right renal vein with no evidence of metastatic lesions. Total right nephrectomy and extirpation of the intravascular tumor of the right renal vein were carried out. Pathological findings showed well-differentiated liposarcoma of the renal sinus. The tumor invaded to the right renal vein and the renal parenchyma.

[Long-term prognosis of incidental renal cell carcinoma--clinical analysis of renal cell carcinoma detected by our health checkup].

PURPOSE: We retrospectively evaluated the characteristics and long-term prognosis of incidentally detected renal cell carcinoma by health checkup. MATERIALS AND METHODS: From January 1987 to December 2005, 556 patients were treated for renal cell carcinoma in our department. Among them, 56 patients were detected by abdominal ultrasonography in health checkup of our health care center. We reevaluated the pathological stage according to 2002 TNM classification and tumor type of renal cell carcinoma according to 2004 World Health Organization histological classification. Survival analysis was determined by Kaplan-Meier's method and log-rank test. RESULTS: Of the patients, 50 were male and 6 were female. The age of the patients ranged 37 to 68 years old at diagnosis (median 54 years). The tumors were located in the right kidney in 22 patients and in the left kidney in 34. Pathologically T1a tumors were found in 40 patients (71%), T1b in 13 (23%), T2 in 2 (4%) and T3b in 1 patients (2%). One case of T3b had N2 and M1 disease. The followup time after the operation ranged 3 to 215 months (median 121 months). Seven patients died of renal cell carcinoma. One of the 7 patients in T1a disease died at 64 months, 4 in T1b at 47, 91, 119, 163 months, 1 in T2 at 39 months and 1 in T3b at 13 months, postoperatively. The cause specific 10-year survival rate was 97% for T1a disease and 57% for T1b (p < 0.01), respectively. CONCLUSION: Most of renal cell carcinomas were T1a disease, which were detected incidentally by health checkup. The cause specific survival rate was significantly higher for T1a disease than for T1b. Our data suggested that early detection was important for good prognosis. The abdominal ultrasonography was only method for detection in routine health checkup and should be broadly implemented.

Novel anatomical findings of the prostatic gland and the surrounding capsular structures in the normal prostate.

With the increase of the patients with prostate cancer, the number of radical prostatectomy increased prominently. Meanwhile, surgeons and pathologists have difficulty regarding appropriate surgical dissection of the prostate and the pathological diagnosis. These problems are derived from uncertainty or misunderstanding about the precise anatomy. In fact, many surgeons are not confident of the structures of the prostatic gland, its surrounding capsules, and the sphincter. Here we investigated the surgical anatomy of the normal prostate to provide beneficial information regarding radical prostatectomy and subsequent pathological diagnosis. A 40 year-old cadaver with a history of sudden cardiac arrest was utilized in this study. Whole pelvic organs were extirpated en bloc and fixed in formalin. Whole mount step sections from the membranous urethra to the seminal vesicle were prepared and histologically examined. It has been reported that the prostatic parenchyma is covered with outside layer (lateral pelvic fascia) and inside layer (prostatic fascia, also known as "capsule"). Here, we show that nearly one third of the anterior surface of the apical region of the prostate (apical prostate) lacks this "capsule". The apical prostate is a mixture of striated muscles, glands, and elastic fibers. Furthermore, the glandular tissue exists within the anterior fibromuscular stroma and some region of the "capsule". Surgeons often try to preserve neurovascular bundles to maintain erectile function; however, other neural tissue was also observed over the entire surface of the prostate. Surgeons must be aware of these complicated anatomical structures when undertaking radical prostatectomy and subsequently diagnosing extra-prostatic extension.

Activation of Notch signaling in tumorigenesis of experimental pancreatic cancer induced by dimethylbenzanthracene in mice.

To establish pancreatic cancer in mice, dimethylbenzanthracene (DMBA) was administered into mice pancreata. The formation of tubular complex lesions was found in the pancreatic sections from 2 weeks after DMBA treatment. Abnormal tubular complex formations with ductal metaplasia were found from 1 month after the administration. By 3 months after DMBA injection into the pancreas, 6 of 10 mice showed visually recognizable tumors with precursor lesions of various types of cell atypia. In contrast, there were no visually or histologically detectable tumors in the placebo-treated animals. The expression profiles of smad 4, cyclin D1 and p53 in the DMBA-induced tumors were similar to those of human pancreatic cancer, suggesting that this would be a useful mouse model for studying the morphological and molecular mechanisms involved in pancreatic carcinogenesis. Immunohistochemical study using specific antibodies revealed that Notch-1 and Hes-1 were expressed in lesions ranging from tubular complexes to carcinoma in these chemically induced pancreatic tumors. Semiquantitative reverse transcription-polymerase chain reaction with microdissection demonstrated that Notch-1 expression was continuous from precursor lesions to carcinoma cells, whereas Pdx-1 expression was attenuated in carcinoma cells compared to precursor lesions. In addition, inhibition of the Notch signaling pathway by the gamma-secretase inhibitor N-(N-[3,5-difluorophenacetyl]-L-alanyl)-S-phenylglycine t-butyl ester reduced pancreatic cancer cell growth. Therefore, Notch signaling is required to form the tubular complexes and its continuous activation might lead to the transition from tubular complexes to premalignant or malignant lesions and carcinoma cell development in the pancreas.

[Histopathologic diagnosis of malignant pleural mesothelioma].

Diffuse malignant mesothelioma is a malignant tumor arising in the pleura from mesothelial cells. It has extremely polymorphous varieties of morphological patterns. Thus, confirming histopathologic diagnosis as mesothelioma, it should need not only histological examination but several methods such as special stain, immunohistochemical study, cytology of pleural effusion and electromicroscopy.

The expression of MUC4 and MUC5AC is related to the biologic malignancy of intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas show heterogeneous proliferations with latent malignancy. Mucins (MUC) are high-molecular-weight glycoproteins, with an aberrant expression profile in various malignancies. Recently, MUC4 and MUC5AC expressions have been demonstrated to correlate with the unfavorable and the favorable prognosis of pancreatic duct cell carcinoma, respectively. However, little is known about these mucin expressions in IPMNs. METHODS: To clarify the role of MUC4 and MUC5AC expressions in IPMNs, the expression profiles of MUC4 and MUC5AC were investigated in 50 lesions from 17 specimens with 16 IPMNs by immunohistochemistry, using each of their specific antibodies. RESULTS: The expression of MUC4 was found in the lesions ranging from adenoma to cancer lesions of IPMNs, whereas it was undetectable in normal and hyperplastic lesions. Frequent expression of MUC4 is found in the higher grade of IPMNs (borderline and cancer lesions; 16/18 lesions, 94%). The differences were independently significant (P < 0.001) when the cutoff point was set between adenoma and borderline IPMNs. Similarly, frequent expression of MUC5AC was detected in the lesions from adenoma to cancer of IPMNs (32/34, 94%), whereas no intense expression was detected in normal or hyperplastic lesions. The significant difference was found when the cutoff point was set between hyperplasia and adenoma of IPMNs (P < 0.001). CONCLUSIONS: These results indicated that the expressions of MUC4 and MUC5AC are potential markers to distinguish adenoma or above malignant lesions of IPMNs from lesser malignant ones, respectively.

Experience of the treatment with gemcitabine, docetaxel, and carboplatin (GDC) chemotherapy for patients with small-cell carcinoma of the prostate.

Small-cell carcinoma of the prostate (SCCP) is a rare entity. Many treatment modalities have been done, but thus far no uniform treatment has been clearly established. We carried out combination chemotherapy with gemcitabine, docetaxel, and carboplatin (GDC) regimen (for two patients with refractory SCCP. Case 1 involved a 53-year-old man diagnosed with SCCP after receiving hormone therapy for prostate cancer (stage D1). Six cycles of GDC chemotherapy was applied. Initially the primary site reduced according with a decline of neuro-specific enolase and with relief of the symptoms; however, bone disease occurred and he died of cancer 13 months after diagnosis of SCCP. Case 2 involved a 69-year-old man complaining of severe anal pain. He underwent a biopsy and a huge prostate tumor showing SCCP was showed. He had pelvic node metastases but no distant lesions, and received four cycles of GDC chemotherapy. He was discharged after receiving subsequent radiotherapy and remained stable for a while; however, he died of possible drug-induced hepatitis. This is the first report of chemotherapy with GDC against patients with SCCP. This regimen raised the possibility that it would intensify the outcome, which had been poorly achieved.

New trends of immunohistochemistry for making differential diagnosis of breast lesions.

Immunohistochemistry is widely used for pathological diagnosis of breast lesions. Other than hormone receptors and HER2/neu analysis for primary breast carcinomas, several markers may be useful for differential diagnoses, although in limited situations. To decide the malignant potential of intraductal proliferative lesions, analysis for the staining pattern of cytokeratins may be a good reference. Most ductal carcinoma in situ cases are diffusely positive for luminal cell markers (CK8, CK18, CK19), but negative for basal cell markers (CK5/6 and CK14). However, usual ductal hyperplasia may show the mosaic staining patterns for any of these markers, which may indicate a heterogeneous cell population in benign lesions. Myoepithelial markers (alpha-SMA, myosin, calponin, p63, CD10) are almost consistently positive for benign papillomas but they do not completely distinguish intraductal papillary carcinomas. Preservation of myoepithelial layer is the diagnostic key when looking at benign sclerosing lesions, including carcinoma with pseudoinvasive structures. E-cadherin is mostly positive for ductal carcinomas but negative for lobular carcinomas. Some of the lobular carcinomas are positive for 34betaE12, but they are consistently negative for CK5/6. Comparison with histopathological findings of hematoxylin and eosin is essential to make proper diagnosis in the individual case.

Time-related changes in computed tomographic appearance and pathologic findings after radiofrequency ablation of the rabbit lung: preliminary experimental study.

PURPOSE: To evaluate correlations between computed tomographic (CT) appearance and pathologic findings after radiofrequency (RF) ablation of lungs and to determine whether CT appearance could predict the extent of the effective therapeutic area. MATERIALS AND METHODS: The lungs of 14 rabbits were subjected to RF ablation and CT scans were obtained immediately and at various intervals thereafter. Four rabbits were killed immediately after the initial CT imaging (n = 4). The remaining 10 rabbits were killed after additional CT scans at intervals of 3 days (n = 2), 1 week (n = 4), 2 weeks (n = 2), and 3 weeks (n = 2) after RF ablation. Pathologic findings were correlated with CT appearance. RESULTS: Immediately after RF ablation, a restricted area of central dense opacity enclosed by an extensive area of ground-glass opacity was noted in the ablated region on CT images. Pathologically, the former corresponded to destructive tissue and the latter corresponded to tissue with some degree of injury. After 1 week, the entire ablated region appeared as a well-demarcated homogeneous dense opacity on CT that corresponded to necrotic tissue and its surrounding rim of granulation tissue on histopathologic examination, indicating that the enclosing extensive area of ground-glass opacity on the initial CT scan represented an ongoing necrosis. Within 2-3 weeks, the ablated region gradually contracted on the CT images, representing a tissue repairing process in which the granulation tissue was encroaching on the inner necrotic tissue. CONCLUSION: Ground-glass opacity of the ablated region on CT immediately after RF ablation represents an ongoing necrosis.

Sex steroid hormone receptors in human skin appendage and its neoplasms.

Sex steroids have been postulated to influence pathophysiology of human skin through various skin appendages. The presence of sex steroid receptors has been also reported in adnexal tumors but its details still remained unknown. Therefore, in this study, we immunolocalized sex steroid receptor protein (estrogen receptor (ER)alpha, ERbeta, progesterone receptor (PR)A, PRB and androgen receptor (AR)) in 23 cases of non-pathological skin (male: 10, female: 13) and in 50 cases of skin adnexal tumors (male 24, female 26; 38 benign and 12 malignant). ERalpha immunoreactivity was detected exclusively in basal cells of sebaceous glands of non-pathological skin. AR and PRB immunoreactivity was detected in both differentiated and basal cells of sebaceous gland. AR and ERbeta immunoreactivity was also detected in sebaceous and eccrine sweat glands but not in outer root sheath of hair follicles. In sebaceous gland neoplasms, the number of ERalpha positive cases was significantly lower in skin appendage neoplasms than non-pathological skin. ERbeta immunoreactivity was not detected in any of sebaceous gland neoplasms examined. There were no significant differences in PRA, PRB and AR immunoreactivity between non-pathological sebaceous gland and its neoplasm. In sweat gland neoplasms, the number of AR positive cases was significantly lower in benign neoplasms than their non-pathological counterpart. Therefore sex steroids are considered to play important roles in regulation of non-pathological skin appendage function and pathogenesis and/or development of its neoplasm. In addition, the status of the great majority of sex steroid hormone receptors was maintained throughout the process of neoplastic transformation of skin appendages, except for AR and ERalpha in sweat and sebaceous gland neoplasms.

Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression.

Cell surface carbohydrates expressed on epithelial cells are thought to play an important role in tumor progression. Previously, we have shown that expression of core 2-branched O-glycans is closely correlated with vessel invasion and depth of invasion in colon and lung carcinomas. In this study, we found that expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1, Core2GnT, is positively correlated with the progression of prostate cancer in human patients. Statistical analysis demonstrated that Core2GnT is an independent predictor for progressed pathological stage (pT3) and for prostate-specific antigen (PSA) relapse. To determine directly the roles of Core2GnT in prostate cancer progression, we set up an experimental tumor model using the LNCaP prostate cancer cell line. Because this line does not express Core2GnT, we established an LNCaP line stably expressing Core2GnT, LNCap-Core2GnT, by transfecting cDNA encoding Core2GnT. When mock-transfected LNCaP cells and LNCaP-Core2GnT were inoculated in the prostate of nude mice, LNCaP-Core2GnT cells produced three times heavier prostate tumors than mock-transfected LNCaP cells. Furthermore, we found that LNCaP-Core2GnT cells adhered more strongly to prostate stromal cells, type IV collagen and laminin than did LNCaP-mock cells, but LNCaP and LNCaP-Core2GnT cells grew almost at the same rate on plates coated with type IV collagen or laminin. These results indicate that Core2GnT is an extremely useful prognostic marker for prostate cancer progression. The results also suggest that acquiring Core2GnT in prostate carcinoma cells facilitates adhesion to type IV collagen and laminin, and this increased adhesion may be a cause for aggressive tumor formation by prostate cancer cells expressing Core2GnT.

In situ androgen producing enzymes in human prostate cancer.

Androgens have been proposed to be actively produced in situ in human prostate cancer. These locally produced androgens have also been considered to play important roles in the pathogenesis and development of prostate cancer. Therefore, it is important to examine the status of this in situ androgen metabolism and/or synthesis in detail in order to improve the clinical response to hormonal therapy in patients diagnosed with prostate cancer. Several studies have previously demonstrated the expression of androgen-producing enzymes such as 5alpha-reductase types 1 and 2, and 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5), in human prostate carcinoma cells. However, their biological significance has remained largely unknown. In this study, we evaluated the immunoreactivities of these steroidogenic enzymes in human prostate cancer obtained from surgery (n = 70), and correlated the findings with clinicopathological features of the patients. 17Beta-HSD5 immunoreactivity was detected in 54 cases (77%), 5alpha-reductase type 1 in 51 cases (73%) and 5alpha-reductase type 2 in 39 cases (56%). 5Alpha-reductase type 2 immunoreactivity was significantly correlated with that of androgen receptor (AR), and 17beta-HSD5 positive cases were significantly associated with clinical stage (TNM stage pT3 vs pT2). These data all suggest that androgen-producing enzymes, such as 5alpha-reductase type 1 and type 2, and 17beta-HSD5 are expressed in a majority of prostate cancers, and are involved in the local production and actions of androgens in prostate cancers.

RM2 antigen (beta1,4-GalNAc-disialyl-Lc4) as a new marker for prostate cancer.

Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, beta1,4-GalNAc-disialyl-Lc(4), defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and >/=4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern >/=4, high Gleason score (>/=8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer.

Post-laminectomy long-term survival of a patient with spinal cord compression secondary to metastatic prostate cancer.

Spinal cord compression is a skeletal-related event in advanced malignancies and is associated with serious morbidity and poor prognosis. Despite the palliative nature of laminectomy treatment, it is important to prevent neurological deficits and relieve pain as a means to improve quality of life. Here we report on a prostate cancer patient with spinal cord compression who became ambulant from paraparesis after he underwent a decompression laminectomy; he survived for 9.5 years with good quality of life.

Inhibition of motility and invasiveness of renal cell carcinoma induced by short interfering RNA transfection of beta 1,4GalNAc transferase.

Human renal cell carcinoma (RCC) has been characterized by remarkable changes in ganglioside composition. TOS1 cells, typical of metastatic RCC, are characterized by predominance of GM2 as monosialoganglioside, and beta 1,4GalNAc disialyl-Lc(4) (RM2 antigen) as disialoganglioside [J. Biol. Chem. 276 (2001) 16695]. In order to observe the functional role of gangliosides in RCC malignancy, TOS1 cells were transfected with short interfering RNA (siRNA) based on open reading frame sequence of beta 1,4GalNAc transferase (beta 1,4GalNAc-T), and its disordered sequence of siRNA (dsiRNA) as control. In siRNA transfectant, beta 1,4GalNAc-T mRNA level and GM2 expression were greatly reduced, whereby GM3 expression appeared. In contrast, RM2 antigen level was unchanged, even though it has the same beta 1,4GalNAc epitope at the terminus. dsiRNA transfectant showed no change of beta 1,4GalNAc-T mRNA and did not express GM3. Concomitant with reduction of GM2 and appearance of GM3, siRNA transfectant showed greatly reduced motility and invasiveness, although growth rate was unaltered. Both transfectants with siRNA and dsiRNA expressed the same level of tetraspanin CD9. Since CD9/GM3 complex is known to reduce integrin-dependent motility and invasiveness [Biochemistry 40 (2001) 6414], it is plausible that motility and invasiveness of siRNA transfectant of TOS1 cells may be reduced by enhanced formation of such complex.

Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study.

Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent (P < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor (P < 0.05, P < 0.01), a higher frequency of HER-2 overexpression (P < 0.025), and more frequent lymph node metastases (P < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains (P < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.

Gene expression profiling identifies a set of transcripts that are up-regulated inhuman testicular seminoma.

Seminoma constitutes one subtype of human testicular germ cell tumors and is uniformly composed of cells that are morphologically similar to the primordial germ cells and/or the cells in the carcinoma in situ. We performed a genome-wide exploration of the genes that are specifically up-regulated in seminoma by oligonucleotide-based microarray analysis. This revealed 106 genes that are significantly and consistently up-regulated in the seminomas compared to the adjacent normal tissues of the testes. The microarray data were validated by semi-quantitative RT-PCR analysis. Of the 106 genes, 42 mapped to a small number of specific chromosomal regions, namely, 1q21, 2p23, 6p21-22, 7p14-15, 12pll, 12p13, 12q13-14 and 22q12-13. This list of up-regulated genes may be useful in identifying the causative oncogene(s) and/or the origin of seminoma. Furthermore, immunohistochemical analysis revealed that the seminoma cells specifically expressed the six gene products that were selected randomly from the list. These proteins include CCND2 and DNMT3A and may be useful as molecular pathological markers of seminoma.