Immunohistochemical localisation of alpha-fetoprotein (AFP) in germ cell tumours: evidence for AFP production by tissues different from endodermal sinus tumour

20 germ cell tumours have been studied with respect to the presence of alpha-fetoprotein (AFP), using the peroxidase-antiperoxidase (PAP) technique. 6 out of 20 tumours contained elements of endodermal sinus tumour (EST) and were AFP positive. 16 tumours were diagnosed either as pure embryonal carcinomas (6) or as mixed germ cell tumours, containing elements of embryonal carcinoma (10). In 3 of these 16 tumours AFP was localised definitely in the embryonal carcinoma cells; in an additional 6, AFP was also detected but it could not be decided whether AFP was present in embryonal carcinoma cells or in EST cells during early differentiation. In 2 of 7 immature teratomas, AFP was shown to be present in cylindric epithelia. All seminomas (4) studied were AFP-negative. These results show that AFP, which occurs regularly in EST, may also be present in embryonal carcinomas as well as in immature teratomas. Thus, it seems that the immunohistochemical demonstration of AFP by the PAP technique is a suitable method of identifying late stages of embryonal carcinoma or early stages of endodermal sinus tumour during the process of differentiation.     

Management of primary intracranial germ cell tumors

Primary intracranial germ cell tumors are rare and usually localized in the pineal and the suprasellar regions. They are divided into the following histologic types: germinoma, teratoma (mature, immature, malignant), choriocarcinoma, embryonal carcinoma, endodermal sinus tumor (yolk sac tumor), and mixed tumors. Clinically, they are manifested with ocular signs or signs of obstructive hydrocephalus. Localized germinomas are treated with radiation therapy and exhibit a relatively good prognosis. Chemotherapy is reserved for disseminated germinomas. Mature teratomas are treated with surgery. The rest of germ cell tumors are managed with various combinations of surgery, chemotherapy, and radiotherapy depending on the tumor type. If the tumors secrete beta-human chorionic gonadotrophin (hCG) or alpha-fetoprotein (FP), these tumor markers can be used to accurately monitor response to treatment. Prognosis is best for germinomas and mature teratomas and worst for choriocarcinomas and embryonal carcinomas.     

Treatment of malignant ovarian germ cell tumors: response to vincristine, dactinomycin, and cyclophosphamide (preliminary report)

From November 1971 to November 1975, 27 patients with malignant germ cell tumors of the ovary (excluding pure dysgerminoma and tumors containing trophoblastic elements) were treated with vincristine, dactinomycin, and cyclophosphamide; 12 patients received other therapy. Fourteen tumors were pure endodermal sinus tumors, two were embryonal carcinomas, 11 were mixed germ cell tumors and 12 were immature teratomas. Of 23 patients with surgically resected disease (Stages I-IIA) only seven have failed. Median follow-up for 16 patients remaining free of disease is 24.5 months. Restaging (second-look) laparotomies were done in 15 patients. Eight were negative. Fifteen of the patients had tumors with endodermal sinus elements. Six of these have failed. Of 16 patients with advanced disease (Stage IIB, III and recurrent), eight have responded to chemotherapy, eight have failed. Median follow-up period for those remaining free of disease is 26.5 months. Six have had negative second-look surgery and one had mature teratoma. Four of eight cases which contained endodermal sinus elements responded to chemotherapy and remain disease-free. Grade 3 hematologic toxicity was seen in eight patients, dose-limiting gastrointestinal toxicity in five patients, dose-limiting neurotoxicity in five patients.     

Malignant Ovarian Germ Cell Tumours: A Survival and Prognostic Analysis

The medical records and histopathology of all ovarian germ cell tumours (OGCT) in a tertiary centre between 1980 and 1996 were reviewed. Response, overall survival (OS), relapse-free survival (RFS) and prognostic factors were analysed. Sixty-seven patients with OGCT were identified and treated, including 33 dysgerminomas, 18 immature teratomas, 10 endodermal sinus tumours, and 6 mixed tumours. Fifty-three patients (79%) received conservative surgery, 24 (36%) had residual disease post-primary surgery, and 43 (64%) had chemotherapy. Complete response was achieved in 62 patients (93%), 4 out of 5 patients who relapsed were successfully salvaged; OS and RFS at 5 years were 89% and 76%, respectively. Advancing stage of disease was the only significant adverse prognostic factor (p=0.0001 for OS, and 0.0003 for RFS at 5 years). Out of 44 women with the potential to conceive following treatment, there were 16 successful pregnancies. None of the children born subsequent to the chemotherapy were reported to have any congenital abnormalities. The review indicates a high cure rate in OGCT with combined surgery and chemotherapy and that conservative surgery and preservation of fertility are feasible.     

Involvement of dysadherin and E-cadherin in the development of testicular tumours

Testicular neoplasms are comprised of a variety of histologically different forms, and their pathogenesis has not been elucidated. Dysadherin is a recently described cell membrane glycoprotein, which has an anticell-cell adhesion function and downregulates E-cadherin. In this study, we examined immunohistochemically the expression of E-cadherin and dysadherin in 120 testicular neoplasms (37 seminomas-26 classic, five spermatocytic and six anaplastic-, 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature and eight immature teratomas and eight non-Hodgkin B-cell lymphomas), clinical stage I. The intensity, the expression pattern and the percentage of neoplastic cell staining was recorded and correlated with the histologic type and vascular/lymphatic invasion. Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas. Dysadherin expression did not correlate with vascular invasion. Increased dysadherin expression was correlated with aberrant E-cadherin expression in most tumours. In 17% of embryonal carcinomas colocalisation of dysadherin and membranous E-cadherin staining was noted. This is the first report on dysadherin expression and its association with E-cadherin in testicular tumours. Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells. In testicular tumours, as in other neoplasms, dysadherin downregulates E-cadherin expression, at least in part.     

DNA copy number changes in malignant ovarian germ cell tumors

Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.     

Histogenetic analysis of ovarian germ cell tumors by DNA fingerprinting.

The histogenesis of ovarian germ cell tumors (11 mature teratomas, three malignant transformations of mature teratomas, two immature teratomas, and four dysgerminomas) was investigated genetically using minisatellite DNA probes 33.15 and 33.6 for person-specific restriction fragment length polymorphism (DNA fingerprint) analysis. The DNA fingerprints of six ovarian teratomas were identical with those of mononuclear cells from each host, while some polymorphic bands observed in the host mononuclear cells were lost in the DNA fingerprints of the other five cases. The cases of malignant transformation of mature teratoma and immature teratoma showed that some polymorphic bands of DNA fingerprints from the host mononuclear cells were absent in the tumor tissues. In four cases with dysgerminomas, the DNA fingerprints of tumors were completely identical with those of the respective host mononuclear cells. The present results suggest that mature cystic teratomas of the ovary arise from germ cells arrested at various stages of meiosis, while immature teratomas are derived from postmeiotic germ cells. Malignant transformation may occur exclusively in the mature teratomas arising from postmeiotic germ cells. Dysgerminomas develop from premeiotic oogonia (primordial germ cells). Thus, DNA fingerprints are a useful and sensitive tool for identifying the pathogenesis of germ cell tumours.     

Human germ cell tumours: expression of gamma-glutamyl transpeptidase and sensitivity to cisplatin.

Previous studies have shown that the enzyme-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours.     

Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report)

Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.     

Embryonal carcinoma of the ovary: a clinicopathologic entity distinct from endodermal sinus tumor resembling embryonal carcinoma of the adult testis.

The clinical and pathologic features of 15 examples of a hitherto undescribed germ cell tumor of the ovary are delineated. This tumor resembles the embryonal carcinoma of the adult testis and may be distinguished from the endodermal sinus tumor on the basis of its histologic and immunohistochemical characteristics. An indirect immunoperoxidase method for the localization of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) was done on formalin-fixed paraffin-embedded tissue from 10 neoplasms; HCG was present in all 10 neoplasms, and AFP was found in seven. HCG was indentified only in cells resembling syncytiotrophoblast, whereas AFP was present only in mononuclear embryonal cells, indicating that the two protein antigens were localized in different cell types. Abnormal hormonal manifestations, consisting of precocious puberty, irregular bleeding, amenorrhea, or hirsutism, were present in nine (60%) of the patients. The actuarial survival for the entire group was 39%; for those with stage I tumors, 50%. We are proposing the term "embryonal carcinoma" for this neoplasm in order to distinuish it from the more common endodermal sinus tumor of the ovary and to emphasize the histologic similarity to embryonal carcinoma of the adult testis.     

Results of the treatment of intracranial germ cell tumors

Presented is a retrospective study of 20 patients with intracranial germ cell tumors who the authors have treated during past 10 years. The cases among these patients included thirteen germinomas, three teratomas, two embryonal carcinomas, and two malignant teratomas. A ventriculoperitoneal shunt was installed in 15 cass and the tumor was surgically removed in four cases. All cases were irradiated with 33 to 61 Gy; in 18 cases, more than half of the total dose was delivered to the whole brain, and in 9 cases, spinal irradiation was given because of a verified CSF dissemination. Chemotherapy was the regimen for four cases. The tumor responded to therapy in 16 (84%) of 19 evaluable cases. Overall, the median and five year survival were 102 months and 83%, respectively. The survival rate was found to vary between the benign group (germinoma, teratoma) and the malignant group (embryonal carcinoma, malignant teratoma, germinoma with STGC) (p less than 0.01).     

Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases

BACKGROUND: Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients. METHODS: The current study is a retrospective review of 74 patients with MOGCT treated by conservative surgery, retaining the uterus and contralateral ovary to preserve ovarian function, with or without chemotherapy. RESULTS: The mean age of the patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31 dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%). There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4 Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients (63.5%). The overall mean follow-up period was 52.1 months. There were 7 recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I disease was 98.2% and that for patients with advanced disease stages was 94.4%. During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these women resumed normal menstrual function on completion of chemotherapy. Fourteen healthy live births were recorded in the chemotherapy group and there were no documented birth defects. There was 1 case of infertility (1.4%). CONCLUSIONS: The surgical approach in young patients with MOGCT confined to a single ovary should aim to preserve fertility. Advanced disease is not usually accompanied by contralateral ovarian disease and should not necessarily contraindicate conservative surgery. The majority of these patients who have received combination chemotherapy resume normal ovarian function and can expect a normal fertility rate and healthy offspring.     

GPR30 is overexpressed in post-puberal testicular germ cell tumors

GPR30 is a 7-transmembrane G protein-coupled estrogen receptor that functions alongside traditional estrogen receptors to regulate cellular responses to 17β-estradiol and environmental estrogens. In this study, we have evaluated by immunohistochemical analysis GPR30 expression in post-puberal testicular germ cell tumours (30 seminomas, 5 teratomas, 12 embryonal carcinomas, and 20 intratubular germ cell tumors). The GPR30 protein expression was detected at high level in all intratubular germ cell tumours, seminomas, and embryonal carcinomas, whereas in teratomas the expression was low. The immunohistochemical data were further confirmed by Western blot analysis. GPR30 protein expression has also been analyzed in GC1 and TCam-2 cell lines, respectively derived from immortalized type B murine spermatogonia and human seminoma. Our results indicate that GPR30 could be a potential therapeutic target; the design of a specific GPR30 inhibitors could be a useful molecular target to block neoplastic germ cells with a high proliferative rate for the treatment of TGCTs.     

Cellular localization of alpha-fetoprotein and human chorionic gonadotropin in germ cell tumors of the testis using and indirect immunoperoxidase technique.

An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha-feto protein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotropho-blastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker.     

Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases.

Fifty-eight immature ovarian teratomas were studied. Neoplams with other germ cell elements (endodermal sinus tumor, choriocarcinoma, and dysgerminoma) were excluded so that the clinical and pathologic features of "pure" immature teratomas could be defined and correlated with the prognosis. The primary tumors and their metastatic growths were graded from 0 to 3. Forty were stage I; nine, stage II; and nine, stage III. The size and stage of teratomas were related to survival, but it was the grade of the primary tumor that best determined the likelihood of extraovarian spread, and it was the grade of the metastases that related best to the subsequent course. Actuarial survival was 63% at 5 years and also at 10 years. Regardless of the grade of the primary tumor, only one of six with grade 0 metastases progressed, and that neoplasms may not have been adequately sampled. Two of five neoplasms having grade 1 metastases did not progress, and two of six patients with grade 2 metastatic growths were living after relatively long intervals. All seven patients with grade 3 metastases died with tumor, none surviving more than 2.1 years. Survival of patients with grade 1, 2, and 3 neoplasms was 81, 60, and 30% respectively. The importance of adequate sampling of primary tumor and metastases for estimating prognosis and determining therapy is stressed.     

Cultured stem-cells from human testicular teratomas: the nature of human embryonal carcinoma, and its comparison with two types of yolk-sac carcinoma

The understanding of differentiation in human teratomas requires a better definition of the phenotype and developmental potential of the stem cells in these tumours. We describe the characterization of 6 new cell lines from human testicular teratomas which are representative of 3 distinct cell types. Cell lines GCT 27, GCT 35, and GCT 48, identified as embryonal carcinoma, comprise epithelial cells which express cytokeratin intermediate filaments and desmoplakins, as determined by indirect immunofluorescence microscopy. A minority of the cells also express vimentin. Most cells in these cultures show surface staining with monoclonal antibodies (MAbs) to stage-specific embryonic antigens SSEA 3 and SSEA 4 but not SSEA 1. Staining with MAb W6/32, which recognizes HLA A,B and C chains in the presence of beta-2 microglobulin, is not above background level. When injected into nude mice, GCT 27 cells form tumours consisting of embryonal carcinoma, somatic tissues, and cells positive in immunocytochemical assays for alphafoetoprotein (AFP) and human chorionic gonadotrophin (HCG); GCT 35 cells form embryonal carcinomas with foci of AFP and HCG-positive cells; and GCT 48 cells form embryonal carcinoma only. A second type of cell (GCT 72) displays some properties of rodent visceral endoderm. GCT 72 cells contain cytokeratin intermediate filaments, but not vimentin, and show very strong staining at cell borders with anti-desmoplakin I + II antibody. At the cell surface, GCT 72 cells express the epitopes recognized by antibodies to SSEA 3, SSEA 4, and SSEA 1; staining with W6/32 is negligible. Levels of AFP in supernatants from GCT 72 cultures are in excess of 500 KIU/I. The tumours formed following inoculation of nude mice with GCT 72 cells are solid yolk-sac tumours, with all cells strongly positive for AFP. A third cell type (GCT 44 and GCT 46), resembles in some ways rodent parietal endoderm. These cells uniformly coexpress keratin and vimentin intermediate filaments, but not desmoplakins. The determinants recognized by MAbs to SSEA 3, 4, or 1 are not detected on the majority of cells in these cultures. In striking contrast to the other teratoma lines, these cells can attach to untreated tissue culture plastic in serum-free medium and may be serially cultivated under these conditions. The tumours formed in nude mice by these 2 cell lines are yolk-sac carcinomas with endodermal sinus tumour histology. Thus, human testicular teratomas consist of epithelial cells which may be nullipotent, pluripotent or committed to extraembryonic endodermal differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Survival and reproductive function after treatment of malignant germ cell ovarian tumors.

PURPOSE: Germ cell ovarian tumors are curable. The possible sequelae of chemotherapy on long-term survivors are still unknown, but these patients may expect normal lives. The aim of this study was to evaluate the outcome and reproductive function in a population of women treated since 1982. MATERIALS AND METHODS: Between 1982 and 1996, 169 women with malignant germ cell ovarian tumors were seen (70 dysgerminomas, 28 endodermal sinus tumors, 24 mixed tumors, and 47 immature teratomas). Seventy-one had advanced or recurrent disease. Fertility-sparing surgery was performed in 138 (81%) women, 81 of whom received postoperative chemotherapy. RESULTS: With a median follow-up of 67 months, the survival rate was 94% for dysgerminoma, 89% for endodermal sinus tumors, 100% for mixed types, and 98% for immature teratoma. For women who were treated conservatively, the survival rate was 98%, 90%, 100%, and 100%, respectively. Two women had adnexal recurrences, and both received salvage treatment. After treatment, all but one postpubertal woman had recovery of menses within 9 months. During follow-up, 12 untreated and 20 treated patients had 55 conceptions. We recorded 40 pregnancies at term, six terminations, and nine miscarriages. Four malformations were observed: one in 14 conceptions of patients who had not received chemotherapy and three in 41 conceptions of treated patients. CONCLUSION: Irrespective of subtype and stage, conservative surgery should become the standard approach to treating most patients with malignant ovarian germ cell tumors. Fertility seems to be only marginally affected by treatments. Miscarriages are in the expected range for the general population. The malformation rate is slightly higher than in the general population, but no significant difference was seen between patients who did and did not receive chemotherapy.     

Teratocarcinoma stem cells

Human teratocarcinomas or mixed germ cell tumours are histologically composed of diverse tissues corresponding to somatic and extraembryonic (trophoblastic and yolk sac) like cells, as well as malignant stem cells. In typical teratocarcinomas these stem cells correspond to embryonal carcinoma cells, ie developmentally pluripotent cells equivalent to embryonic cells from the early stages of development. These cells have the capacity to differentiate and give rise to non-proliferating terminally differentiated tissue. Occasionally embryonal carcinoma cells can give rise to more differentiated stem cells which have the phenotype and the restricted developmental potential of choriocarcinoma and yolk sac carcinoma cells, or less commonly to somatic cell malignancies, indistinguishable from typical carcinomas, sarcomas, melanoma or lymphomas. Malignant transformation of benign somatic tissues in teratomas can also give rise to malignant stem cells, which all have a somatic cell phenotype. The biology and the clinical presentation as well as the response to chemotherapy of germ cell tumours depend on the nature of stem cells that form their proliferative compartment and account for the malignancy of these tumours.     

Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP

During the last 6 1/2 years, serum AFP has been determined by radioimmunoassay in 387 patients with germ cell tumors of the gonads and extragonadal sites. The histological appearances of all these neoplasms were carefully reviewed. Highly elevated levels of serum AFP were noted in patients with tumors containing endodermal sinus (yolk sac) tumor elements irrespective of the location of the neoplasm or presence or absence of metastatic disease. There was good correlation between the presence and quantity of endodermal sinus (yolk sac) tumor elements within the primary tumor or its metastases and elevated levels of serum AFP. All patients with tumors composed of pure seminoma or dysgerminoma, and teratoma, had normal serum AFP levels. Slightly elevated levels of serum AFP up to 60 ng/mg (upper limit of normal 20 ng/ml) were noted in a few patients with testicular tumors composed of pure embryonal carcinoma, whereas patients with tumors composed of or containing endodermal sinus (yolk sac) tumor elements had serum AFP levels that could be measured in 100's or 1000's of ng/ml. Serum AFP was elevated only in patients with active disease. Serum AFP was determined in 81 patients with gonadal tumors of non germ cell origin and was normal in all these patients. Serum AFP is a very good tumor marker in patients with germ cell tumors composed of or containing endodermal sinus (yolk sac) tumor, irrespective of their location. Serial serum SFP determinations can be used for diagnostic purposes, for monitoring the results of treatment, and for early detection of metastases and recurrences. Serial serum AFP determination is a useful procedure in all patients with germ cell neoplasms and is highly recommended.