Elevated prostate markers in metastatic small cell carcinoma of unknown primary.

Numerous ectopic hormones and markers have been described in small cell carcinoma of the lung as well as in extrapulmonary small cell carcinomas. The authors report a case of a patient with metastatic small cell carcinoma of unknown primary who had very high prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) levels. Results of multiple prostate examinations, as well as blind biopsies, were normal. His course was significantly longer than that of the usual patient with extensive small cell carcinoma. At autopsy the prostate showed only mild benign prostatic hypertrophy. There are no previous reports in the literature of abnormal prostate markers in small cell carcinomas. Physicians should be aware of the increasing complexity and the unusual biologic markers associated with neuroendocrine carcinomas. In some of these cases, the tumors ability to produce an ectopic product may portend an improved prognosis.     

Prostatic carcinoma metastatic to bone: sensitivity and specificity of prostate-specific antigen and prostatic acid phosphatase in decalcified material

Decalcified bone marrow biopsies containing metastatic tumor from 36 patients were stained for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) using the avidin biotin complex (ABC) immunoperoxidase technique. Of these patients, 22 had known prostate primaries, ten had known nonprostatic, and four female patients had unknown primaries. Prostate-specific antigen was identified in 86% (19/22) of the metastatic prostatic carcinomas. Prostatic acid phosphatase was present in only 36% (8/22). None of the patients with nonprostatic primaries or unknown primaries showed positive staining for either antigen (0/14). This study indicates that immunoperoxidase staining for PSA is very sensitive and specific in the diagnosis of metastatic prostate carcinoma, while PAP was less sensitive using decalcified bone marrow specimens. We believe that immunostaining with PSA should be of great value in diagnosis of prostatic carcinoma metastatic to the bone.     

The histogenesis of small cell carcinoma of the prostate. An immunohistochemical study

Small cell carcinomas of the prostate are rare. A few reported cases have manifested morphologic and functional neuroendocrine characteristics, and it has been suggested that these tumors are derived from the argentaffinic/argyrophilic cells normally present in the prostate. The authors have recently studied three cases of primary prostatic small cell carcinoma in which the small cell component developed during the course of progression of "regular" prostatic adenocarcinoma, and reflected a terminal aggressive phase of the disease. Immunoperoxidase staining for prostate-specific acid phosphatase (PSAP) showed positivity in the adenocarcinoma but absence in the small cell component of each tumor. The association of small cell carcinoma with prostatic adenocarcinoma indicates that in considering the histogenesis of prostatic small cell carcinoma, a specific neuroendocrine cell of origin need not be implicated.     

Prostatic carcinoma: a multivariate analysis of prognostic factors.

Tissue specimens from 150 patients with localised prostatic carcinomas and 116 patients with prostatic carcinomas with distant metastases were analysed for histological grade (WHO and Gleason) and immunoreactivity for prostate acid phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After stratification for the presence or absence of distant metastases, multivariate regression analysis revealed that WHO grading was the most powerful independent prognosticator, followed by age and prostate acid phosphatase expression. There was a trend towards reduced survival with decreasing prostate-specific antigen reactivity. The Gleason system showed poor prognostic ability. The analysis predicted reduced survival in the presence of extensive neurone-specific enolase reactivity, mostly because of one case of small-cell carcinoma.     

Secondary colonic adenocarcinoma of the prostate histologically mimicking prostatic ductal adenocarcinoma

PURPOSE: To study the clinical presentation and pathological features of secondary colonic adenocarcinoma of the prostate. MATERIALS AND METHODS: Six cases of colonic adenocarcinoma extending into the prostate were retrieved from the surgical pathology and autopsy files of the period 1985-1999. Immunostaining for prostatic acid phosphatase (PAP), prostate specific antigen (PSA), cytokeratin 7 (CK7), cytokeratin 20 (CK20) and carcinoembryonic antigen (CEA) was carried out in all cases. Clinical charts were also reviewed. RESULTS: Secondary colonic carcinoma spread into the prostatic stroma and along the prostatic ducts. In all four surgical cases, patients with a known history of rectal carcinoma presented with symptoms of urinary obstruction after 12 to 36 months of being free of recurrent or metastatic disease. In three surgical cases the secondary carcinoma involved the prostatic urethra in a form mimicking endometrioid carcinoma, which led to an incorrect diagnosis of prostatic endometrioid carcinoma in one case. The tumor cells were immunoreactive to CK20 and CEA and not reactive to CK7, PAP and PSA. CONCLUSIONS: Colonic carcinoma involving the prostate may mimic prostatic duct carcinoma due to the ductal and urethral involvement. Using a panel of immunostaining and clinical history is helpful in the differential diagnosis.     

Evaluation of PAP and PSA gene expression in prostatic hyperplasia and prostatic carcinoma using northern-blot analyses,in situ hybridization and immunohistochemical stainings with monoclonal and bispecific antibodies

In this report we have investigated levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) gene expression in prostatic carcinoma (Ca) and benign prostatic hyperplasia (BPH) specimens. Northern-blot analyses of total prostatic mRNA indicated that there was a tendency towards lower amounts of PAP mRNA and PSA mRNA in the Ca specimens than in the BPH specimens, although, because of the great variation in the expression levels of both mRNAs, these differences were not statistically significant. In situ hybridization analyses clearly showed that both PAP and PSA mRNAs were confined to the columnar epithelial cells and that stromal cells were devoid of these mRNAs. In addition, PAP and PSA mRNAs were more abundant in BPH tissue than in adjacent Ca tissue within the same specimen. The levels of PAP and PSA enzymes were analyzed immunohistochemically using a bispecific antibody having high affinity for both PAP and PSA, and the results were compared with those obtained using monoclonal anti-PAP and anti-PSA antibodies. All 3 antibodies stained only epithelial cells and BPH tissue consistently gave more intense staining than Ca tissue. Furthermore, the anti-PSA and the bispecific anti-PAP-PSA antibodies stained well or moderately differentiated Ca tissues more strongly than poorly differentiated Ca tissues. No PSA staining was detected in 3 and no PAP staining in 5 of the moderately or poorly differentiated carcinomas (grades II or III). Our results show that, in comparison with BPH tissue, prostatic Ca tissue is associated with significantly lower levels of mRNAs coding for the prostatic marker enzymes PAP and PSA, as well as with lower concentrations of these enzymes. Furthermore, dedifferentiation of prostate Ca is associated with a decrease in the level of intraprostatic PSA.     

Prostate Cancer Old Problems and New Approaches

Diagnostic and prognostic markers for prostatic cancer (PCa) include conventional protein markers (e.g., PAP, PSA, PSMA, PIP, OA-519, Ki-67, PCNA, TF, collagenase, and TIMP 1), angiogenesis indicator (e.g., factor VIII), neuroendocrine differentiation status, adhesion molecules (E-cadherin, integrin), bone matrix degrading products (e.g., ICPT), as well as molecular markers (e.g., PSA, PSMA, p53, 12-LOX, and MSI). Currently, only PSA is used clinically for early diagnosis and monitoring of PCa. The histological differential diagnosis of prostatic adenocarcinoma includes normal tissues such as Cowper's gland, paraganglion tissue and seminal vesicle or ejaculatory duct as well as pathological conditions such as atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia and sclerosing adenosis. A common PCa is characterized by a remarkable heterogeneity in terms of its differentiation, microscopic growth patterns and biological aggressiveness. Most PCa are multifocal with signi ficant variations in tumor grade between anatomically separated tumor foci. The Gleason grading system which recognizes five major grades defined by patterns of neoplastic growth has gained almost uniform acceptance. In predicting the biologic behavior of PCa clinical and pathological stages are used as the major prognostic indicators. Among the cell proliferation and death regulators androgens are critical survival factors for normal prostate epithelial cells as well as for the androgen-dependent human prostatic cancer cells. The androgen ablation has been shown to increase the apoptotic index in prostatic cancer patients and castration also promotes apoptotic death of human prostate carcinoma grown in mice. The progression of PCa, similarly to other malignancies, is a multistep process, accompanied by genetic and epigenetic changes, involving phenomenons as adhesion, invasion and angiogenesis (without prostate specific features).     

The accumulation of angiostatin-like fragments in human prostate carcinoma.

PURPOSE: Angiostatin, a potent inhibitor of angiogenesis and, hence, the growth of tumor cell metastasis, is generated by a proteolytic enzyme from plasminogen. However, its localization and specific enzymes have yet to be ascertained in human tissue. EXPERIMENTAL DESIGN: To elucidate the generation and the localization of angiostatin in prostate carcinoma, we examined angiostatin generation in a panel of human prostate cancer cell lines and performed immunohistochemistry with the antibodies to angiostatin and prostate-specific antigen (PSA), a potent proteolytic enzyme of angiostatin in 55 cases of prostate carcinoma. RESULTS: We demonstrated that the lysates of human prostate carcinoma cell lines could generate angiostatin-like fragments from purified human plasminogen but could not generate angiostatin in the absence of exogenous plasminogen. The fragmented proteins were reacted with the monoclonal antibody specific for plasminogen lysine-binding site 1 (LBS-1). Immunohistochemically, the intracytoplasmic immunostaining of LBS-1 was positive in 87.3% (48 of 55) of prostate carcinoma cases, and the immunostaining of miniplasminogen was negative in all cases. There was a significant relationship between the positive immunostaining of LBS-1 and Gleason score (P = 0.0007). The intracytoplasmic immunostaining of PSA was positive in 37.0% (20 of 54) of prostate carcinoma cases, but there was no significant relationship between the expression of PSA and Gleason score, or between the positive immunostaining of LBS-1 and PSA. CONCLUSIONS: These findings suggest that angiostatin is generated by prostate carcinoma cells and is accumulated within the cytoplasm. In addition, the generation of angiostatin-like fragments was correlated with tumor grade; however, PSA may not be the only enzyme for angiostatin generation in human prostate carcinoma.     

Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract

BACKGROUND: Although many articles have been published regarding neuroendocrine tumors (NET) and neuroendocrine carcinomas of both low- and high-grade malignancy (NEC) of the genitourinary tract, the histologic diagnosis and therapeutic strategies for treating these entities remains difficult. In the current study the author discusses the significant differences between NET and NEC of the urinary bladder and the prostate, including therapeutic consequences. METHODS: Four hundred eighty neoplasms of the urinary bladder and prostate with a small cell pattern were analyzed not only on slides stained with hematoxylin and eosin but also by means of immunohistochemical stains demonstrating a neuroendocrine origin. The avidin-biotin complex method was used with the following markers: MIB-1, chromogranin A (Chr A), synaptophysin (SNP), cytokeratin (CK) 34betaE12, CK20, androgen receptor (AR), and prostate specific antigen (PSA). RESULTS: Twenty tumors of the urinary bladder and 26 of the prostate demonstrated a diffuse neuroendocrine pattern. Only two patients were found to have a low-grade NEC of the prostate with a low proliferative index but strong expression of neuroendocrine markers. All other patients with small cell neuroendocrine carcinomas of the bladder and prostate demonstrated extremely high proliferation activity (>80%) and expressed Chr A and SNP. CK34betaE12, 20, PSA, and AR were not found to be expressed. The mean survival time was 6.9 months. Fourteen of 20 patients with NEC of the urinary bladder died of the disease and 19 of 24 patients with prostatic NEC died. The therapy for urinary bladder NEC was repeated transurethral resection and antiandrogen therapy was given for NEC of the prostate. Only one patient was treated with chemotherapy, which to the author's knowledge currently is the only treatment for NECs of the genitourinary tract. CONCLUSIONS: Undifferentiated carcinomas of the urinary bladder and prostate should be analyzed not only by means of hematoxylin and eosin but also by immunohistochemical staining for Chr A and SNP to demonstrate a neuroendocrine origin. Because the prognosis of small cell NECs is very poor, pathologists should indicate in their final report the peculiarities of small cell NECs of the prostate and the urinary bladder with special emphasis on different therapeutic strategies.     

Small cell carcinoma of the major salivary glands. An immunohistochemical study.

Small cell carcinomas of the major salivary glands are rare tumors, accounting for less than 1% of malignant neoplasms at these sites. To date, approximately 41 such tumors have been described. They recently have been classified into two groups, based on the ultrastructural presence or absence of intracytoplasmic neuroendocrine (NE) granules, "small cell neuroendocrine carcinoma" and "small cell ductal carcinoma". This study concerns 11 primary small cell carcinomas that had been previously studied ultrastructurally; it was undertaken to determine whether these lesions possessed a neuroendocrine phenotype, using a battery of immunohistochemical stains. Antibodies to epithelial membrane antigen (EMA), cytokeratin (CK), Leu 7, vimentin (VIM), synaptophysin (SYN), chromogranin (CHR), and neuron-specific enolase (NSE) were employed, with the avidin-biotin-peroxidase complex technique and paraffin sections. All tumors in this study expressed at least one neuroendocrine marker. In eight tumors EMA was found; CK was present in all 11 cases, seven of which demonstrated focal paranuclear staining. Leu 7 was seen in eight tumors, VIM was expressed in two cases, SYN was found in three tumors, and CHR was detected in three neoplasms. Anti-neuron-specific enolase labeled eight tumors. From the preceding data one may conclude that all small cell salivary gland carcinomas have neuroendocrine characteristics, even though dense core granules cannot be demonstrated in some of them ultrastructurally.     

The use of antikeratin antibodies in the immunohistochemical distinction between neuroendocrine (Merkel cell) carcinoma of the skin, lymphoma, and oat cell carcinoma

Paraffin sections of formalin-fixed tumor samples from 26 patients with neuroendocrine (Merkel cell) carcinoma of the skin (NECS) were studied immunohistochemically with three monoclonal antibodies to low molecular weight keratin (MAB-K) and with antibodies to leukocyte common antigen (LCA), neurofilament (NF), neuron-specific enolase (NSE), S100 protein (S100), and chromogranin (CGN), to investigate the relative diagnostic value of these antibodies. Samples from 20 lymphomas, 10 non-oat cell undifferentiated carcinomas, 10 oat cell carcinomas, and 10 melanomas served as controls. Keratin was found in 25 of the 26 NECS and in all undifferentiated and oat cell carcinomas. A ball-like immunostaining for keratins, resembling an inclusion body was seen only in cases of NECS and some carcinoids. Neurofilament, NSE, and CGN were expressed by fewer NECS than was keratin and all NECS were negative for LCA and S100. None of the lymphomas and melanomas contained detectable keratin, NF, NSE, or CGN. Only the lymphomas stained with LCA. Only the melanomas were S100-positive. It is concluded that keratin is the most useful single discriminating marker in the separation of neuroendocrine (Merkel cell) carcinoma of the skin from lymphoma, melanoma and, when the characteristic inclusion-like pattern is seen, from metastatic oat cell carcinoma.     

A comparative study on expression of prostatic inhibin peptide, prostate acid phosphatase and prostate specific antigen in androgen independent human and rat prostate carcinoma cell lines

Prostatic inhibin peptide (PIP), consisting of 94 amino-acid residues is synthesized and secreted by the prostate gland. Previous studies on immuno-histochemical localization of PIP in primary prostatic tumor and their metastasis, have documented the value of this peptide as a tumor marker for diagnosis of prostate cancer (PCa). The present study was undertaken to compare the expression of PIP with that of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in androgen independent human PCa cell lines (PC-3, DU-145 and TSU-Prl) by immunoperoxidase technique. The results of the study indicated that the staining for PIP was more intense than that of PSA and PAP. The PSA staining was either weakly positive (PC-3) or totally absent (TSU-Prl and DU-145) while PAP staining was intense in PC-3 and moderate in the other two human cell lines. The intense staining observed for PIP in all of the androgen independent cell lines suggests that the synthesis and secretion of PIP is not primarily dependent on androgens. Furthermore, expression of these markers in Dunning rat cultured adenocarcinoma cell lines and tumors were studied. Positive staining for all three human tumor associated antigens (PIP, PSA and PAP) cross-reacting with the Dunning rat PCa cell lines and the tumors, suggest the suitability of this model for preclinical screening of various therapeutic agents.     

Prise en charge des carcinomes neuroendocrines de prostate : revue de la littérature

Neuroendocrine prostate carcinoma is a rare entity causing both diagnostic and therapeutic issues. There are basically four histological forms (adenocarcinoma with neuroendocrine differentiation, carcinoid tumors, small cell neuroendocrine carcinomas, large cell neuroendocrine carcinomas), which can be pure or mixed associated with prostatic carcinoma. There is no consensus on the management or the prognosis of these various tumor subtypes. We conducted a literature review aiming to determine the potential therapeutic implications.     

Immunohistochemical diagnosis of metastasizing prostatic carcinomas

Metastases of 47 known prostatic carcinomas were subjected to the unlabelled immunoperoxidase-procedure to localise prostaticacid-phosphatase (PAP) and prostatic-specific antigen (PSA). In bone-marrow, lymph-node, lung and liver metastases PAP was found in 64% and PSA in 78%. There was no significant difference between the intensity of staining in primary and metastatic neoplasm. In poorly differentiated metastases of prostatic adenocarcinomas less intense staining for PAP and PSA was found. The data suggest that the demonstration of PAP and PSA is a practical and sensitive test for the prostatic origin of a clinically and histologically unclassifiable metastasis.     

Small cell carcinoma of the kidney. A clinicopathologic, immunohistochemical, and ultrastructural study

Three cases of primary small cell carcinoma of the kidney with light microscopic, immunohistochemical, and electron microscopic findings are reported. Two patients died of disseminated disease 8 months and 1 year, respectively, after the diagnosis and the third was free of tumor after 18 months. Immunohistochemical studies revealed keratin immunostaining of tumor cells in two cases and staining for neuron-specific enolase in the third. The third case also showed a few dense neurosecretory granules at the ultrastructural level. Although no strong conclusions regarding histogenesis can be drawn, this study indicates that small cell carcinoma of the kidney exists and does not necessarily exhibit a neuroendocrine differentiation. Small cell carcinoma of the kidney must be considered in the differential diagnosis of malignant renal tumor, especially in cases in which a large necrotic tumor is present. Based on the few cases presented in this study and on the one previously reported case, small cell carcinoma of the kidney appears to be an aggressive tumor.     

Study of the hormone-refractory prostate cancer clinical practice in an anti-cancer center]

We have examined 82 patients with hormonoresistant prostate cancer in a retrospective study. Bone and lymph node metastases were observed in 94% and 30% of patients respectively. However, the visceral metastases were frequent: liver (17%), lung (7%), bone marrow (4%), meningitis (4%). PSA is constantly high but 28% of the patients have elevated NSE, which is correlated with lymph node or visceral metastases. ACE is elevated in 27% of cases. Objective and palliative effect of chemotherapy is marked for weekly doxorubicin, prednisone with mitoxantrone and etoposide associated with platin-salts for prostatic carcinoma with neuroendocrine differentiation. This study suggests the presence of different subpopulations of patients with specific evolutive patterns, thus further specific therapy should be evaluated.     

Neuron-specific enolase as a new tumor marker

Enolase is a glycolytic enzyme widely distributed in each mammalian tissue and consists of three distinct subunits alpha, beta, and gamma. In the brain enolase exhibits three dimetric isozymic forms: alpha alpha, alpha gamma and gamma gamma. The gamma protein subunit has recently been found to be identical with the nervous system-specific and species-nonspecific protein, 14-3-2; therefore, alpha gamma and gamma gamma types of enolase were characterized as neuron-specific enolase (NSE). NSE has been also detected in the pituitary gland, thyroid gland, adrenal medulla and pancreas, all of which contain neuroendocrine cells. Recently NSE was observed by immunostaining or radioimmunoassay in neuroendocrine tumor such as glucagonomas, insulinomas, gut carcinoids, medullary thyroid carcinomas or neuroblastomas. Furthermore, small cell carcinoma of the lung which has been known to frequently exhibit neuroendocrine properties was found to produce NSE. In this paper NSE as a tumor marker in various cancers was evaluated by immunostaining or enzyme immunoassay which was developed by a co-worker Kato. The data revealed that serum NSE was clinically useful as a tumor marker, especially a monitoring marker of disease extent. NSE productions were also observed in adenocarcinoma of the colon or the lung and large cell carcinoma of the lung as well as small cell carcinoma of the lung and the esophagus, all of which were considered to share the biochemical features of neuroendocrine tumor. The evidence challenges a speculation that small cell carcinoma of the lung has an origin separated from the other histological types of lung carcinoma. In this meaning NSE is an important tumor marker for both clinical medicine and basic research.     

Vascular endothelial growth factor (VEGF) expression in prostatic tumours and its relationship to neuroendocrine cells.

Vascular endothelial growth factor (VEGF) expression was examined by immunohistochemistry in 45 prostatic carcinoma specimens and ten benign prostatic tumours (BPH). The majority of carcinoma specimens exhibited cytoplasmic staining for VEGF and showed a trend of increasing expression with dedifferentiation (2p = 0.003). Immunoreactive VEGF was also seen in the prostatic carcinoma cell lines, the order of staining intensity was PC3 > DU145 > LNCaP. Intense granular cytoplasmic staining for VEGF was observed in neuroendocrine-like cells which were seen focally in many of the prostatic specimens. Consecutive sections were incubated with a chromogranin A antibody to confirm the neuroendocrine phenotype of these cells. A significant correlation (P < 0.0001) between the total number of intensely stained VEGF-positive cells and chromogranin A-positive cells was found. A subpopulation of neuroendocrine-like cells also showed intense immunoreactivity for transforming growth factor alpha (TGF-alpha). A correlation was observed (2p = 0.0092) between the intensity of VEGF and TGF-alpha immunostaining in carcinoma cells which were not of neuroendocrine differentiation. The presence of these two angiogenic factors may aid the neovascularisation of carcinomas and their increased expression in tumour-associated neuroendocrine cells may contribute to a more aggressive phenotype.     

An unusual variant of prostatic adenocarcinoma with metastasis to testis.A case report

Ductal adenocarcinoma of the prostate is considered to be a rare variant of prostatic adenocarcinoma when compared to the more common acinar adenocarcinoma. We report here a case of ductal adenocarcinoma of the prostate in a 68-year old man who presented with complaints of abdominal pain, retention of urine and hematuria of one month duration. Clinical examination showed prostatomegaly. The serum Prostate Specific Antigen (PSA) value was raised to 79ng/mL. Histopathological and immunohistochemical evaluation of resected specimen of prostate revealed ductal adenocarcinoma of the prostate. The patient was lost to follow up and presented four years after the initial diagnosis with metastasis to the bone and testis. Though prostatic cancers have the ability for wide spread dissemination, metastasis to testis is rare. Immunohistochemical staining with PSA and Prostatic Acid Phosphatase (PAP) can help in establishing prostatic nature of the neoplasm. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors. Keywords: Prostate, ductal adenocarcinoma, metastasis, testis.     

Leu-7 in small cell neoplasms. An immunohistochemical study with ultrastructural correlations

In an effort to delineate the distribution of the Leu-7 antigen in small cell neoplasms, 283 paraffin-embedded examples of such tumors were studied immunohistochemically. These included 125 malignant lymphomas, 94 neuroendocrine carcinomas, 13 adenocarcinomas, 14 squamous carcinomas, four malignant melanomas, six neuroblastomas, four nephroblastomas (Wilms' tumors), six primitive neuroectodermal neoplasms, three "Askin" tumors, ten Ewing's sarcomas, and four embryonal rhabdomyosarcomas. Histologic diagnoses were verified by the use of electron microscopic study or independent immunostains. Overall, 44% of small cell neuroendocrine carcinomas expressed Leu-7, whereas nonendocrine carcinomas were uniformly nonreactive for this determinant. All neuroblastomas yielded immunopositivity, as did three primitive neuroectodermal tumors, three rhabdomyosarcomas, two "Askin" tumors, one nephroblastoma, one Ewing's sarcoma, and one malignant melanoma. None of the small cell lymphomas were Leu-7 positive. These results suggest that Leu-7 is a specific neuroendocrine marker in cases of small cell carcinoma, but its sensitivity is lower than that of other "endocrine" determinants. Reactivity patterns for Leu-7 in other small cell tumors demonstrate no specificity for any given line of cellular differentiation. However, the shared expression of this antigen by neuroblastomas, neuroectodermal tumors, Ewing's sarcomas, and Wilm's tumors contributes further to the hypothesis that these neoplasms may be related histogenetically.