G K Jacobsen

Rigshospitalet, København, Capital Region, Denmark

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Publications (36)143.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Prompted by the recently reported expression of POU5F1 (OCT3/4) in epididymis, a panel of markers for carcinoma in situ (CIS) testis and testicular germ cell tumours (TGCT), including AP-2γ(TFAP2C), NANOG, OCT3/4, KIT, placental-like alkaline phosphatase (PLAP), M2A/PDPN and MAGE-A4 were examined by immunohistochemistry or in situ hybridisation in urogenital epithelia, which may interfere with detection of CIS cells in semen. In addition to OCT3/4, the expression of AP-2γ and NANOG or their variants was detected in urogenital epithelia, while other CIS markers, including PLAP/alkaline phosphatase were absent. A combination of immunocytological staining for AP-2γ or OCT3/4 and rapid cytochemical alkaline phosphatase reaction was subsequently developed. This approach was tested in 22 patients with TGCT. In 14 patients (63.6%), double stained cells were found and thus the method was proven suitable for the detection of CIS cells in semen. In conclusion, transcription factors related to pluripotency and undifferentiated state of cells, which most likely have several variants or modifications, are unexpectedly detected using currently available antibodies in urogenital epithelial cells which may be shed into semen. Combining the immunohistochemical nuclear markers with a rapid cytochemical alkaline phosphatase reaction for detection of CIS cells in ejaculates may provide a more reliable diagnostic method.
    Andrologia 02/2011; 44(2):78-85. · 1.55 Impact Factor
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    ABSTRACT: Since Jan. 1, 1976 practically all new cases of germ cell tumours of the testis in Denmark have been included in the Danish Testicular Carcinoma Study (DATECA), permitting detailed registration of data concerning histology and stage at the time of diagnosis. The incidence of carcinoma of the testis in Denmark continues to be high with a crude rate of 8 to 9/100000 males per year. During the past 5 years the size of the primary tumours has decreased. Parallel to this, the rate of metastatic spread has decreased for seminoma, while no such change has been observed for non-seminomatous tumours. Data are presented on histology and stage for 1058 consecutive patients.
    Acta Oncologica. 07/2009; 23(4).
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    ABSTRACT: To examine the occurrence and prognostic significance of intratubular germ cell neoplasia (IGCN) and microinvasive germ cell tumour (MGCT) in tissue adjacent to testicular germ cell tumours (TGCT) in adults. The study was based on two Danish studies of adult patients with stage I TGCT and included 255 patients. Of 106 patients with seminoma, 75 [71%, 95% confidence interval (CI) 61, 79] had IGCN without MGCT and nine (8%, CI 4, 15) had both IGCN and MGCT. Of 149 patients with non-seminoma, 62 (42%, CI 34, 50) had IGCN without MGCT, and 32 (22%, CI 15, 29) had both IGCN and MGCT. Non-seminomas with a seminoma component were more often associated with MGCT (23 of 54 testes, 43%, CI 29, 57) than were non-seminomas without this component (nine of 95 testes, 10%, CI 4, 17) (P < 0.000 05, Fisher's exact test). Relapse-free survival was not influenced by the concomitant presence of the two precursor stages in the testes (P = 0.36, and P = 0.19, log rank test, respectively). MGCT was a relatively frequent finding in testes adjacent to a macroscopic TGCT. However, neither IGCN nor MGCT predicted relapse for patients with stage I TGCT.
    Histopathology 06/2004; 44(6):547-54. · 2.86 Impact Factor
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    ABSTRACT: Spermatocytic seminoma is a rare germ cell derived tumour of the testis that occurs mainly in older men. We analysed the expression of recently discovered markers for germ cell differentiation and the mitosis-meiosis transition in order to define the antigen profile for diagnostic purposes and to clarify the biology and histogenesis of spermatocytic seminoma. Twenty-five spermatocytic seminomas were examined for immunohistochemical expression of germ cell-specific onco-fetal antigens and proteins involved in regulation of germ cell division, DNA repair and differentiation. The panel included Chk2, p19INK4d, p53, MAGE-A4, KIT, TRA-1-60, neurone-specific enolase and placental-like alkaline phosphatase. Four of these proteins/antigens have never before been investigated in spermatocytic seminoma. Proteins highly expressed in gonocytes and spermatogonia, such as Chk2, MAGE-A4 and neurone-specific enolase, were consistently present in spermatocytic seminoma. Antigens expressed in embryonic germ cells but not in the normal adult testis, e.g. TRA-1-60, were undetectable, with the exception of p53 protein, which was demonstrated in 80% of cases. A proto-oncogene p19INK4d, which is involved in the transition from mitotic to meiotic division in germ cells, was not detected in spermatocytic seminoma. The investigation provided new information concerning the expression of Chk2, MAGE-A4, neurone-specific enolase and p19INK4d in spermatocytic seminoma. The pattern of expression is highly consistent with the origin of spermatocytic seminoma from a premeiotic germ cell, which has lost embryonic traits and has committed to spermatogenic lineage but has not yet passed the meiotic checkpoint, most probably from the spermatogonium of the adult testis.
    Histopathology 04/2003; 42(3):217-26. · 2.86 Impact Factor
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    ABSTRACT: Serum lactate dehydrogenase isoenzyme 1 catalytic concentration (S-LD-1) was measured at the time of orchiectomy in 104 patients with nonseminomatous testicular germ cell tumors (NSTGCT) clinical stage I who participated in a randomized study comparing surveillance after orchiectomy (group I) and radiotherapy (group II). For 68 patients, S-LD-1 was measured in a serum sample before or on the day of the orchiectomy. Twenty-seven patients (40%) had elevated S-LD-1; median 102 U/L (range 41-335). For the remaining 36 patients. S-LD-1 was measured in a serum sample after orchiectomy: 8 of these patients (22%) had elevated S-LD-1. S-LD-1 was normalized shortly after surgery in most patients with a preorchiectomy elevated S-LD-1. Fifteen of the 68 patients relapsed: 9 out of 27 with an elevated S-LD-1 and 6 out of 41 patients with normal S-LD-1 (p = 0.13, Fisher's exact test). In group 1, those with a preoperatively elevated S-LD-1 had a lower 8-years' relapse-free survival than those with a normal S-LD-1 (40% vs. 80%, p = 0.003, log-rank test). The role of S-LD-1 in the staging, prognostication and monitoring of patients with NSGCT clinical stage I should be further explored in a large, prospective study.
    Acta Oncologica 02/2001; 40(4):536-40. · 2.87 Impact Factor
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    ABSTRACT: From 1985 to 1988, 261 unselected patients entered a nationwide Danish study of surveillance only for testicular seminoma stage I. The median follow-up time after orchidectomy was 48 months, range 6-67 months. 49 patients relapsed (19%). Sites of relapse were paraaortic lymph nodes in 41 patients, pelvic lymph nodes in 5, inguinal lymph nodes in 2 and lung metastases in 1 patient. The median time to relapse was 14 months, range 2-37 months. The 4-year relapse-free survival was 80%. 37 of the relapsing patients (76%) had radiotherapy as relapse treatment. Of these patients, 4 (11%) had a second relapse and received chemotherapy. 1 died of disseminated seminoma. Of the relapsing patients, 12 (24%) had chemotherapy as relapse treatment because of bulky (11 patients) or disseminated disease (1 patient). None of these patients have had a second relapse. However, 2 patients died of infection due to chemotherapy-induced neutropenia. Thus, there have been three seminoma-related deaths (1.1%). The testicular tumour size had an independent prognostic significance. The 4-year relapse-free survivals were 94, 82 and 64% for tumours < 3, 3 to < 6 and > or = 6 cm, respectively. Patients with tumours > or = 6 cm will now be given prophylactic radiation treatment, whereas we will continue to use surveillance only after orchidectomy for patients with tumours < 6 cm.
    European Journal of Cancer 01/1993; 29A(14):1931-4. · 5.06 Impact Factor
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    ABSTRACT: From December 1980 to January 1984, all patients with stage I nonseminomatous testicular cancer in Denmark entered a randomized trial comparing surveillance only with radiotherapy after orchiectomy. One hundred fifty patients were assessable for the final analysis. Relapse occurred in 23 patients in the surveillance group and in 11 patients in the radiotherapy group. Radiotherapy completely prevented retroperitoneal relapse; 14 retroperitoneal relapses occurred in the surveillance-only group. All relapsing patients in the surveillance-only group are without evidence of disease with a median observation time after chemotherapy of 67 months. Two of the patients with relapse in the radiotherapy group died with disease; the others are alive without evidence of disease, with a median observation time after relapse treatment of 72 months. In the surveillance group, four relapses occurred later than 2 years after orchiectomy; only one such late relapse occurred in the radiotherapy group. Four of the retroperitoneal relapses occurred without concomitant increase in the serum marker levels (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]). It is concluded that surveillance only should replace radiotherapy after orchiectomy as standard treatment for clinical stage I nonseminomatous testicular cancer. Improved methods for control of retroperitoneal relapses, especially of embryonal carcinomas, are needed.
    Journal of Clinical Oncology 10/1991; 9(9):1543-8. · 18.04 Impact Factor
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    ABSTRACT: 156 patients with stage I non-seminomatous testicular germ cell tumour entered a countrywide randomized study comparing the effect of postoperative irradiation of retroperitoneal lymph nodes with surveillance only. A total of 150 patients were included in this investigation of factors associated with increased risk of relapse. Thirty-four patients (23 per cent) had a relapse, i.e. 11/67 (16 per cent) in the former and 23/83 (28 per cent) in the latter group. Histopathological studies of the orchidectomy specimens were performed in order to identify features associated with relapse. Pure embryonal carcinoma and vascular involvement were significantly associated with increased risk of relapse. Thus, the relapse rate in the observation group in patients with pure embryonal carcinomas was 50 per cent (5/10) and 36 per cent (19/53) in all patients with tumours with vascular involvement.
    Apmis 05/1990; 98(4):377-82. · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 156 patients with stage I non-seminomatous testicular germ cell tumour entered a countrywide randomized study comparing the effect of postoperative irradiation of retroperitoneal lymph nodes with surveillance only. A total of 150 patients were included in this investigation of factors associated with increased risk of relapse. Thirty-four patients (23 percent) had a relapse, i.e. 11/67 (16 per cent) in the former and 23/83 (28 per cent) in the latter group. Histopathological studies of the orchidectomy specimens were performed in order to identify features associated with relapse. Pure embryonal carcinoma and vascular involvement were significantly associated with increased risk of relapse. Thus, the relapse rate in the observation group in patients with pure embryonal carcinomas was 50 per cent (5/10) and 36 per cent (19/53) in all patients with tumours with vascular involvement.
    Apmis 01/1990; 98:377-382. · 2.07 Impact Factor
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    ABSTRACT: Carcinoma in situ in the contralateral testis was diagnosed in 27 of 500 patients (5.4%) with unilateral testicular germ cell cancer. Eight of the 27 patients received intensive chemotherapy for spread of their initial testicular cancer. Follow up biopsy studies did not detect changes of carcinoma in situ in any of these patients, and none developed a contralateral testicular tumour (observation time 12-88 months). Of the remaining 19 patients with carcinoma in situ, seven developed contralateral testicular cancer. The estimated risk of developing invasive growth was 40% within three years and 50% within five years. None of the 473 patients without carcinoma in situ detected by screening biopsy developed contralateral testicular cancer (observation time 12-96 months). No serious complications arose from the biopsy procedures. All patients with unilateral testicular germ cell cancer should be offered biopsy of the contralateral testis.
    British medical journal (Clinical research ed.) 12/1986; 293(6559):1398-401.
  • The Lancet 02/1985; 1(8420):98. · 39.06 Impact Factor
  • M Jacobsen, G K Jacobsen
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    ABSTRACT: The influence of different fixatives on the antigenicity of alpha-fetoprotein (AFP), albumin, prealbumin, transferrin, ferritin, human chorionic gonadotropin (HCG), specific pregnancy beta 1-glycoprotein (SP1) and human placental lactogen (HPL) was studied. No single fixative was superior for all the antigens investigated. For intracellular antigens the best all-around fixatives were, however, 10% buffered formalin, 4% buffered paraformaldehyde, 10% formol-calcium and ethanol acetic acid (EA), cold processed. The preferable fixatives were for AFP: Bouińs fixative, B-5 and EA; for albumin: 10% formol-calcium; for prealbumin: Zambonis fixative and B-5; for transferrin: EA; for ferritin: 10% buffered formalin, 4% buffered paraformaldehyde, Lilliés fixative, Zambonis fixative and EA; for HCG: Bouińs fixative and B-5; for SP1: Lilliés fixative and EA; and for HPL: 4% buffered paraformaldehyde and Lilliés fixative. The preservation of extracellular antigens was different from the above mentioned intracellular ones. Thus fixation in 10% buffered formalin gave poor results while the coagulant fixatives such as Bouińs fixative, B-5 and Clelands fixative in general showed good preservation of the antigenicity of the extracellular antigens.
    Acta pathologica, microbiologica, et immunologica Scandinavica. Section A, Pathology 12/1984; 92(6):461-8.
  • G K Jacobsen, B Nørgaard-Pedersen
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    ABSTRACT: Recently, placental alkaline phosphatase (PLAP) has been suggested as a tumour marker in patients with seminomas (S), since elevated serum levels of PLAP were found with high frequency in these patients. The present immunoperoxidase study of 33 testicular germ cell tumours was undertaken to localize PLAP in the various types of these tumours as well as in the carcinoma-in-situ (CIS) pattern. Eighteen out of 19 (95%) S were PLAP positive compared to nine out of 14 (64%) non-seminomas (NS). In the NS the positive staining reaction was localized to tumour components of embryonal carcinoma (EC) in six cases, of choriocarcinoma (CC) in one and of S in two, while components of yolk sac tumour and teratoma were PLAP negative. The number of positively stained cells in S was much higher than in EC. The staining reaction was pronounced in the syncytiotrophoblast of CC and in some syncytiotrophoblast-like cells present in S. The staining reaction product was mainly confined to the cell membrane in the positive tumour types. In 20 out of 24 cases with CIS various numbers of CIS cells were PLAP positive, while PLAP was not found in normal germinal epithelium. Sixty three per cent of S patients had serum values above 1.0 micrograms/l, while such values occurred in 21% of NS patients. The tissue staining pattern for PLAP was found to correspond to the preoperative serum value. On the basis of these findings it is concluded that PLAP may be a useful marker in patients with S. Serum levels of PLAP may be used diagnostically in patients with testicular tumours and for monitoring therapy and detection of recurrences in patients with S. For optimal utility of this marker, determinations of serum profiles of PLAP are recommended. Finally, demonstration of PLAP in CIS indicates a functional relationship between CIS and S supporting the hypothesis that CIS is the precursor state of these tumours.
    Acta pathologica, microbiologica, et immunologica Scandinavica. Section A, Pathology 10/1984; 92(5):323-9.
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    ABSTRACT: Prognostic factors in carcinoma of the testis were studied in 1058 adult patients treated in Denmark from 1976 to 1980. Separate analyses of the prognostic factors were carried out within the subgroups formed by a classification of the patients according to main histologic type (seminoma, non-seminoma) and the clinicoradiologic stage (I, II and III). The prognosis was measured by relapse-free survival (stage I and II), and survival (stage II and III). The prognostic value of 19 clinical and histologic parameters was evaluated using logrank tests and multiple regression analyses. An elevated HCG level and the size of retroperitoneal metastases were associated with a significantly adverse prognosis for seminoma in stage II. For non-seminomas the following parameters had a significant influence on the prognosis. Stage I: postoperative HCG level, local invasion and number of mitoses. Stage II: size of retroperitoneal metastases, postoperative HCG level, tumour size and local invasion. Stage III: presence of liver or lung metastases, postoperative HCG level, presence of choriocarcinoma or endodermal sinus tumour, and age.
    Acta radiologica. Oncology 02/1984; 23(4):271-85.
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    ABSTRACT: Since Jan. 1, 1976, nearly all new cases of testicular germ cell tumours have been included in the Danish Testicular Carcinoma Study (DATECA), and have been monitored by the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). During the first five years, 1058 patients participated in the investigation, but only 603 of these patients were followed by preoperative as well as postoperative marker determinations in serum. The overall prevalence of marker positivity, i.e. elevated preoperative values for AFP and/or HCG, was 8 per cent for seminoma patients and 60 per cent for non-seminoma patients. Elevated levels of serum AFP and HCG were correlated to the presence of endodermal sinus tumour and choriocarcinoma elements, respectively, in the primary tumour. The presence of increased marker concentration in serum was correlated stage (higher percentage in higher stages) and to prognosis (marker negative patients had a better prognosis than marker positive patients). Marker production by seminoma patients seems to indicate a poor prognosis, especially for HCG producing seminomas.
    Acta radiologica. Oncology 02/1984; 23(4):287-94.
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    ABSTRACT: In the first five-year period of the Danish Testicular Carcinoma Study (DATECA) 1058 consecutive testicular germ cell tumours were examined. Of these, 554 were seminomas comprising 515 of typical type, 26 anaplastic and 13 spermatocytic; 497 were non-seminomas comprising 145 pure tumours and 352 mixed tumours of various types. Among the various subtypes of non-seminomas embryonal carcinoma (EC) was recorded in 87 per cent, endodermal sinus tumour (yolk sac tumour; EST) in 22 per cent, teratoma (T) in 55 per cent and choriocarcinoma (CC) in 17 per cent. Only very few tumours were pure EST or pure CC. Five tumours were recorded as 'others or uncertain'. The tumours were graded with regard to various histologic features. Moderate and severe necrosis, bleeding, and a large number of mitoses were significantly more frequent in non-seminomas. The presence of tumour tissue at the resection margin was also more frequent in non-seminomas. Tumours with a largest diameter of less than 2.5 cm had already caused metastases in 16 per cent of the seminomas and 29 per cent of the non-seminomas. Increasing size of the tumours was associated with increasing frequency of metastatic disease but this association was not directly proportional. Distribution of the various histologic types according to the stage of disease varied. Thus, 78 per cent of the seminomas presented in stage I while 54 per cent of the non-seminomas had localized disease. Anaplastic seminomas were distributed similarly to the non-seminomas while all spermatocytic seminomas, with one exception, were recorded as stage I. Of non-seminomatous subtypes pure EC was associated with the highest frequency of stage III, followed by mixed tumours containing CC components. Although the present series is large the heterogeneity of germ cell tumours demands further investigation of larger numbers to confirm some of the findings.
    Acta radiologica. Oncology 02/1984; 23(4):239-47.
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    ABSTRACT: Since Jan. 1, 1976 practically all new cases of germ cell tumours of the testis in Denmark have been included in the Danish Testicular Carcinoma Study (DATECA), permitting detailed registration of data concerning histology and stage at the time of diagnosis. The incidence of carcinoma of the testis in Denmark continues to be high with a crude rate of 8 to 9/100 000 males per year. During the past 5 years the size of the primary tumours has decreased. Parallel to this, the rate of metastatic spread has decreased for seminoma, while no such change has been observed for non-seminomatous tumours. Data are presented on histology and stage for 1058 consecutive patients.
    Acta radiologica. Oncology 02/1984; 23(4):249-53.
  • Acta Oncologica - ACTA ONCOL. 01/1984; 23(4):239-247.
  • Acta Oncologica - ACTA ONCOL. 01/1984; 23(4):287-294.
  • Acta Oncologica - ACTA ONCOL. 01/1984; 23(4):249-253.

Publication Stats

797 Citations
143.41 Total Impact Points

Institutions

  • 1991–2011
    • Rigshospitalet
      • • Department of Pathology
      • • Department of Oncology
      København, Capital Region, Denmark
  • 2003–2004
    • Copenhagen University Hospital Gentofte
      Hellebæk, Capital Region, Denmark
  • 1993
    • Aarhus University Hospital
      • Department of Oncology
      Århus, Central Jutland, Denmark
  • 1990
    • Aalborg University Hospital
      Ålborg, North Denmark, Denmark
  • 1979–1984
    • Herlev Hospital
      • Department of Pathology
      Herlev, Capital Region, Denmark
  • 1983
    • University of Copenhagen Herlev Hospital
      Herlev, Capital Region, Denmark