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Objective To investigate the clinical characteristics of women with Stage I primary mucinous epithelial ovarian carcinoma (mEOC) and evaluate the impact of uterus-preserving surgery (UPS) in terms of survival prognosis. Methods A regional multi-institutional retrospective study conducted between January 1986 and March 2017 by reviewing records of the Tokai Ovarian Tumor Study Group. Clinical and pathologic data and survival outcomes were assessed for women with Stage I primary mEOC. The baseline imbalance between women with and those without UPS was adjusted by an inverse probability of treatment weighting method using the propensity score (PS) of independent clinical variables. Results Among 4730 women with malignant ovarian tumors, 185 had Stage I primary mEOC and were included in the study. The mean age was 47.6 years (range 12-87 years), and 56 (30.3%) women underwent UPS. After PS-based adjustment, women in the UPS group did not have a poorer prognosis regarding overall survival (P=0.776) or recurrence-free survival (P=0.683). Even after age stratification, there was no statistical difference in survival outcomes between the UPS and non-UPS groups. Conclusion UPS was not associated with decreased survival and may be a treatment option for women with Stage I primary mEOC irrespective of age.

Endometrial clear-cell carcinoma (ECC) is relatively rare. The expression of diagnostic markers in this disease is similar to that of clear-cell carcinoma, but the molecular carcinogenic events and therapeutic targets are mostly unknown. MET gene amplification has been reported in various cancers, including ovarian clear-cell carcinomas; however, the MET gene status has not previously been examined in ECC. We performed real-time quantitative PCR (QPCR) and fluorescence in situ hybridization (FISH) to analyze the MET gene statuses of 12 ECC cases. We found MET amplifications in two cases (2/12; 16.7%) by both methods. Of the 12 cases, 9 were pure clear-cell carcinomas, and 3 were mixed types that included mixes with endometrioid carcinomas in 2 cases, and the remaining case was a heterologous-type carcinosarcoma that primarily consisted of a clear-cell carcinoma component and a scarce chondrosarcoma component. Both of the MET amplification cases were mixed; one contained endometrioid features, and the other chondrosarcoma features. This is the first report to analyze the statuses of the MET gene in ECCs, and the two mixed cases exhibited amplifications that are shared with ovarian clear-cell carcinomas. Further studies with larger numbers of cases are necessary to reveal the relationship between ECC and MET amplification.

Ovarian cancer is the most lethal gynecologic malignancy, and clear cell adenocarcinoma of the ovary (OCCA), in particular, has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Chromobox (CBX) 7 is a polycomb repressive complex 1 component that prolongs the lifespan of normal human cells by downregulating the INK4a/ARF expression which promotes cell-cycle progression. However, recent reports studying the relationship between CBX7 expression and patient survival have differed regarding the tumor cell origins, and the precise role of CBX7 in human carcinomas remains obscure. In this study, we analyzed CBX7 expression by immunohistochemistry in 81 OCCA patients and evaluated its association with their clinical outcomes. Both the overall and progression-free survival rates of the CBX7-positive patients were significantly shorter than those of the CBX7-negative patients (p < 0.05). CBX7 knockdown experiments using two OCCA cell lines, TOV21G and KOC-7C, revealed that cell viability was significantly reduced compared to the control cells (p < 0.001). Expression microarray analysis revealed that apoptosis-related genes, particularly tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were significantly upregulated in CBX7 knockdown cells (p < 0.01). We further confirmed that CBX7 knockdown resulted in TRAIL-induced apoptosis in the OCCA cells. Thus, in this study, we showed for the first time that CBX7 was associated with a decreased OCCA prognosis. We also successfully demonstrated that the TRAIL pathway is a novel target for CBX7 expression modulation in these cells, and therapeutic agents utilizing the TRAIL pathway may be particularly effective for targeted OCCA therapy.

Aim: The effect of systematic retroperitoneal lymphadenectomy (SRL) remains controversial in patients with advanced epithelial ovarian cancer (aEOC) who are optimally debulked. Material and Methods: Demographic and clinicopathologic data were obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2009. All patients were divided into two groups. Group A (n = 93): (i) patients did not undergo SRL; and (ii) lymph node exploration or sampling was optional. Group B (n = 87): patients underwent SRL. Survival curves were calculated using the Kaplan–Meier method. Differences in survival rates were analyzed using the log–rank test. Results: All pT3–4 aEOC patients were optimally debulked (residual tumor

We studied the morphologic, immunologic and clinical features of 14 cases of primary non-lymphoblastic non-Hodgkin's lymphomas of the mediastinum. The patients ranged in age from 3 to 76 years, with a median age of 28 years. According to the Ann Arbor classification, 71% of our cases were in an early stage. Three cases were in Stage I, eight in Stage II, one in Stage III and two in Stage IV (one with multiple hepatic lesions and another with bone marrow involvement). The patients were heterogeneous in terms of the disease and were therefore histologically classified into three categories: diffuse large B cell lymphoma with sclerosis (DLS; n = 8); large cell anaplastic lymphoma (LC-Ana; n = 5); and low grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma; n = 1). DLS was the most common group and was characterized as CD5-, CD10-, CD19+, CD20+, CD21- and CD22+. Imprint smears showed azurophilic granules in the cytoplasm of the tumor cells of three of four DLS cases. All of the six cases examined were negative when tested for Epstein-Barr virus (EBV) sequences after hybridization with the EBV internal repeat probe. DLS and MALT lymphoma cases were of a B-lineage lymphoma of the thymus, while most of the LC-Ana cases were of a T-lineage lymphoma. Patients with non-lymphoblastic non-Hodgkin's lymphomas had a relatively favorable prognosis compared with lymphoblastic lymphoma (P0.01 by the generalized Wilcoxon test). There was no significant difference in the survival between non-lymphoblastic non-Hodgkin's lymphoma and Hodgkin's disease (P0.05 by the generalized Wilcoxon test).

Wnt signaling activates the canonical pathway and induces the accumulation of non-phosphorylated beta-catenin (NPBC) in the nucleus. Although this pathway plays an important role in the maintenance of haematopoietic stem cells as well as in oncogenesis, the significance of nuclear NPBC remains unclear in malignant haematopoiesis. This study examined the expression of nuclear NPBC in bone marrow specimens from 54 and 44 patients with de novo acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), respectively. On immunohistochemistry with an anti-NPBC antibody, the nuclei were positively stained in 22 and 18 of AML and MDS specimens, respectively. Staining of nuclear NPBC was associated with AML subtypes (M6 and M7), low complete remission (CR) rate, and poor prognosis. Nuclear NPBC was also associated with a high score when using the International Prognostic Scoring System (IPSS) for MDS and with -7/-7q and complex karyotypes. These findings suggest that in situ detection of nuclear NPBC by immunohistochemistry could provide new insights into the pathogenesis and prognosis of AML and MDS.

Background and Objectives There were a few reports of a large number of patients with clear cell adenocarcinoma (CCA) of the ovary because of the low incidence of CCA. This study compared the clinical factors affecting long-term survival of patients with CCA to those with serous cystadenocarcinoma (SCA). Methods One hundred and seventy-eight CCA and 311 SCA patients treated between 1987 and 2000 were retrospectively evaluated. Differences in survival rates were calculated using log-rank test and Cox's proportional hazards analysis was used to identify independent prognostic factors. Results The ratio of stage I was significantly higher than that of SCA. There was no significant difference of 8-year survival rate in each stage between CCA and SCA. However, the patients with stage IIIb or IIIc CCA showed significantly worse prognosis than those with SCA. Positive peritoneal or ascitic cytology, the presence of residual tumor, more than 100 ml ascites were demonstrated to have the significant impact on survival by univariate analysis. Multivariate analysis demonstrated that stage, more than 100 ml ascites, and the presence of residual tumor were significant prognostic factors of CCA overall survival. Conclusions Distribution of stage and substage differed between CCA and SCA in this study. Thus, substaging is quite important for comparison of prognoses between histologies, and CCA showed poorer prognoses than serous adenocarcinoma in stages IIIb and IIIc. J. Surg. Oncol. 2006;94:138–143. © 2006 Wiley-Liss, Inc.

Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCI-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed RhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoB indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC.

Background: To investigate whether using a new concept of relative probability for prostate cancer (RPpca) can increase sensitivity and specificity in detecting prostate cancer. Methods: For 217 patients with total prostate-specific antigen (PSA) level of 4–20 ng/mL, prostate volume and free to total PSA (F/T) ratio were measured. From the fitted curves between positive predictive values for prostate cancer and age, prostate volume, total PSA or the F/T ratio, each function predicting prostate cancer was determined. RPpca defined by the combined functions of age, prostate volume, total PSA and F/T ratio was calculated for each individual patient. The probability of prostate cancer was also calculated, using logistic regression analysis (LRPpca). Receiver-operating characteristic analysis was performed to elucidate the areas under the curve (AUC), sensitivities and specificities and cutoff values of the conventional and new parameters. Finally, we investigated the applicability of the above parameters in the other patient group using a different PSA assay kit (AxSYM). Results: Although RPpca had the largest AUC in the total PSA range of 4–20 ng/mL, it did not reach statistical significance between RPpca and F/T ratio or LRPpca. The cutoff values of F/T ratio, LRPpca and RPpca were determined as 0.15, 0.12 and 0.20, respectively. Using these cutoff values in AxSYM data, RPpca had the highest sensitivity (91%) and specificity (57%). Conclusions: RPpca can provide more precise information to avoid unnecessary biopsy than LRPpca or F/T ratio. RPpca could be valuable to decide whether to perform prostate biopsy when using various PSA kits.

Recently, tissue engineering has become available as a regenerative treatment for bone defects. However, the evaluation of its success is limited to histological analysis, and its effects on mechanical hardness remain to be investigated. This study investigated mechanical strength in support of histological findings, specifically for tissue-engineered bone with mesenchymal stem cells (MSCs) and platelet-rich-plasma (PRP). Initially, teeth were extracted, and bone defects on both sides of the mandible were prepared with a trephine bar. The defects were implanted by using the following graft materials: 1) PRP, 2) PRP and dog MSCs (dMSCs), 3) autogenous bone (PCBM), 4) bone substitute (Bio-Oss), and 5) control (defects only). After 2, 4, 8, and 12 weeks of implantation, the defects were histologically assessed to examine their mechanical properties. According to histological observations, the dMSCs/PRP groups had well-formed mature bone compared with the control (defects only), Bio-Oss, and PRP groups. The Vickers hardness test values were 8 (control), 9 (PRP), not detected (Bio-Oss), 11 (PCBM), and 17 (dMSCs/PRP) after 2 weeks. Therefore, tissue-engineered bone can be used for early stage bone regeneration from the viewpoint of histology and mechanical properties.

Testicular germ cell cancer is a common cancer in young adults and its incidence has risen dramatically over the past several decades in Western countries. Because RET finger protein (RFP), which belongs to the large B-box RING finger protein family, has been reported to be expressed in different stages of spermatogenesis, we investigated its expression in testicular germ cell tumors. These comprised 13 pure seminomas, five pure non-seminomatous germ cell tumors (NSGCT) and seven mixed germ cell tumors, four of which contained seminomatous component. In normal adult testis, the expression of RFP was strong in the germ cells, particularly in spermatogonia and primary spermatocytes. RFP immunoreactivity was seen uniformly and specifically in 12 of the 13 pure seminomas examined. It was also detected in seminomatous components of mixed germ cell tumors, whereas pure NSGCT were negative for RFP expression. The expression of RFP in male germ cells and seminomas together with the lack of its expression observed in highly aggressive NSGCT suggested that RFP could be associated with the regulation of germ cell proliferation and/or histological-type of germ cell tumors.

Background: Clarithromycin (CAM) may have certain indirect effects on Helicobacter pylori (H. pylori) other than its inhibitory activity on bacterial growth, as indicated in other infections with Gram-negative micro-organisms. In the present study, we examined the effects of lower concentrations of CAM on the release of heat shock protein B (HspB), one of the major antigenic proteins from H. pylori cells, as well as the changes in humoral immune response and histological degree of antral gastritis in patients who received eradication therapy with CAM. Methods: The H. pylori strain 26695 and three CAM-resistant clinical isolates were cultured in broth with and without CAM (2–500 ng/mL). Expression of H. pylori proteins was examined by two-dimensional (2D)-electrophoresis followed by N-terminal amino acid sequencing. Changes in host immune response and histological degree of antral gastritis were monitored in patients with peptic ulcer disease who received H. pylori eradication therapy. Results: 2D electrophoresis showed 26 spots in extracellularly released proteins with different profiles from those in cytoplasmic proteins. The release of HspB increased after incubation with CAM (30–500 ng/mL) in all three H. pylori clinical isolates tested. Patients with failed H. pylori eradication after triple therapy with CAM, but not those with failed eradication after dual therapy without CAM, showed an increase in serum IgG1 and IgG2 antibodies against HspB along with a decrease in the degree of neutrophil and H. pylori colonization density in tissue sections. Conclusions: CAM may induce a humoral immune response against H. pylori and a decrease in gastric mucosal inflammation through up-regulation of the release of HspB from the bacteria in infected patients.

BACKGROUND Perineural invasion is one of the important prognostic factors for patients with bile duct carcinoma, and extensive surgery has not always improved their prognosis. It is necessary, therefore, to investigate not only clinicopathologic characteristics but also molecular mechanisms in patients with perineural invasion. The authors studied the relation between perineural invasion in patients with bile duct carcinoma and the expression of glial cell line-derived neurotrophic factor (GDNF), GDNF family receptor α1 (GFRα1), and RET receptor tyrosine kinase, which are expressed in both central and peripheral nerve tissues. METHODS Immunohistochemical staining of GDNF, GFRα1, and RET was performed in 58 paraffin embedded tissue sections, including 38 sections from patients with bile duct carcinoma with perineural invasion and 20 sections from patients with bile duct carcinoma without perineural invasion. The migration of cells that expressed GDNF was analyzed by cocultivation with cells that expressed both RET and GFRα1. RESULTS Moderate to strong staining of GDNF in tumor cells was observed more frequently in the sections with perineural invasion compared with the sections without invasion (P < 0.05), whereas GFRα1 expression in the same sections was not correlated with perineural invasion. RET expression was undetectable in specimens of bile duct carcinoma. Conversely, RET and GFRα1 expression were detected consistently in peripheral nerve tissues. An in vitro cell migration assay revealed that the migration of cells that expressed GDNF was enhanced by cocultivation with cells that expressed RET and GFRα1. The cell migration was also enhanced by the conditioned media from GDNF-treated cells that expressed RET and GFRα1. CONCLUSIONS The results suggest that GDNF expression in tumor cells and GFRα1 and RET expression in peripheral nerve tissues may play a role in perineural invasion in patients with bile duct carcinoma through chemoattraction among these molecules. Cancer 2002;94:167–74. © 2002 American Cancer Society.

The placental leucine aminopeptidase (P-LAP)/oxytocinase whose serum level increases with gestation is thought to contribute to the maintenance of normal pregnancy. P-LAP mRNAs are expressed in various tissues other than the placenta. In this study, we identified P-LAP protein in the brain. In contrast with the placenta where a significant portion of P-LAP is released, the enzyme was localized in the membrane fraction in brain and PC12 cells and no soluble form of the enzyme was detected. When PC12 cells were differentiated into neuronal cells by nerve growth factor (NGF), a significant increase in the expression level of P-LAP in the cell was observed. As in the case of insulin treatment of 3T3-L1 adipocytes, treatment of PC12 cells with forskolin caused the translocation of the enzyme from intracellular vesicle to the cell surface plasma membrane. In addition, P-LAP was shown to degrade several bioactive neuropeptides such as Met-enkephalin and dynorphin A (1–8). These results suggest that P-LAP plays an important role in the regulation of neuronal cell function in the brain.

Syndecan-4 is a transmembrane protein bearing heparan sulfate chains, involved in anticoagulation and focal adhesion formation. Here, we revealed that syndecan-4 was expressed in the fetal vessels in the placental labyrinth by in situ hybridization and immunohistochemical staining. At 17.5 gestational days, the area of degenerated fetal vessels in the placental labyrinth was more diffuse and larger in Synd4(-/-) embryos than wild-type controls. Calcium and fibrin(ogen) depositions in the degenerated vessels were also more extensive and more severe in the placentas of Synd4(-/-) embryos. These findings suggest that syndecan-4 deficiency impairs the fetal vessels in the placenta, probably due to a deficit in the anticoagulation mechanism. This article is the first report demonstrating that among a large number of core proteins of heparan sulfate proteoglycans, a defect of a single core protein caused impaired anticoagulation in a specific site. © 2000 Wiley-Liss, Inc.

The RET finger protein (RFP), which belongs to the B box zinc finger protein family, has a tripartite motif consisting of a Ring finger, a B box finger and a coiled-coil domain. The RET finger protein becomes oncogenic when its tripartite motif is fused with the tyrosine kinase domain of the RET protein. This study examined the RFP expression in normal and tumor tissues by immunohistochemistry. RFP was detected in the nuclei of various cells, including peripheral and central neurones, hepatocytes, adrenal chromaffin cells and male germ cells. Among them, RFP was expressed at high levels in male germ cells such as primary spermatocytes and round spermatids, and formed a perinuclear cap structure in primary spermatocytes. On the other hand, high levels of cytoplasmic expression of RFP were observed in some plasma cells as well as solitary plasmacytoma and multiple myeloma. These results suggested that different nuclear/cytoplasmic distributions of RFP might play a role in the regulation of growth or differentiation of different cell types.

1. The aim of the present study was the evaluation of human gastric ulcer healing and intractability from the viewpoint of connective tissue components. 2. Based on investigations of clinical status, we divided 78 patients with a gastric ulcer into three groups. All patients underwent gastrectomy and group I consisted of 17 patients operated on for bleeding or perforation, group II consisted of 37 patients operated on for an accompanying gastric carcinoma and group III consisted of 24 patients operated on for ulcer intractability. 3. We evaluated, in resected specimens, angiogenesis by Azan-Mallory staining and fibroplasia by applying proliferating cell nuclear antigen (PCNA) immunostaining. The inflammatory grade and fibrosis at the ulcer base were also evaluated by haematoxylin-eosin and Azan-Mallory staining. 4. Microvessel counts in group III were significantly lower than those in group I and II (P < 0.05). The PCNA labelling index of fibroblasts in group III was significantly lower than that in groups I and II (P < 0.05). The inflammatory grade was severe and fibrosis was excessive in group III. 5. From these results, it is suggested that the reduced angiogenesis and decline in fibrous cell proliferation are important factors contributing to gastric ulcer intractability.

Bone marrow (BM) and peripheral blood (PB) involvement in 10 patients with mantle cell lymphoma (MCL) was analysed by a polymerase chain reaction (PCR)-mediated RNase protection assay. The complementarity determining regions (CDR)-III of all 10 MCLs examined was amplified efficiently with consensus V(H) and J(H) primers by PCR. and BM and/or PB involvement was evaluated by RNase protection assay in all 10 patients examined. Our assay showed BM and/or PB of the entire group to have neoplastic cells at presentation, despite the fact that eight patients were found to have BM and/or PB involvement on the basis of morphological examination and/or surface marker analysis. We also examined minimal residual disease (MRD) after conventional chemotherapy, and detected MRD in a patient in complete remission (CR). Although previous studies have shown that t(11;14) breakpoint amplification by PCR was only applicable to about 30-40% of cases, the present study indicates that CDR-III is a useful molecular marker and the PCR-mediated RNase protection assay is a good tool for the evaluation of MRD in MCL. It is suggested that BM and PB of MCL patients are quite frequently involved at presentation and even after conventional chemotherapy at the molecular level.

hCDC47 is a human member of the MCM family, which has been implicated in the regulatory machinery causing DNA to replicate once per cell cycle. We examined its protein expression and localization in normal human tissues, using immunostaining with polyclonal antibodies. Positive nuclei were found in the proliferative components of lymph nodes, bone marrow, epidermis and mucosa. Immunohistochemical analysis was also performed for 3 types of cutaneous keratinocytic tumor originating from same cell type but showing different grades of malignancy. In seborrheic keratosis, a benign condition, cells with hCDC47-positive nuclei were located in the outermost layers of the tumor lobules, while in Bowen's disease, carcinomas in situ and squamous-cell carcinomas, they were present throughout the lesions. The percentages of hCDC47-positive cells were 65.4% in squamous-cell carcinomas, 60.9% in Bowen's disease, 12.6% in seborrheic keratosis and 3.9% in normal epidermis (n = 5 in all cases). Further expansion of the analysis to include malignant tumors from several other organs revealed that all malignant lesions tested contained more nuclear hCDC47-positive cells than their normal counterparts. Our findings indicate that hCDC47 plays a role in normal and neoplastic cell growth in vivo and that hCDC47 immunolocalization could be used as an index of cell proliferation in tissue sections.

We investigated the expression of interleukin-6 (IL-6) mRNA in tumours from 21 patients with B-cell non-Hodgkin's lymphoma (NHL). Total RNA, extracted from diagnostic tissue specimens, was subjected to semi-quantitative analysis for IL-6 mRNA by the reverse transcription-polymerase chain reaction (RT-PCR). The amount of IL-6 mRNA ws semi-quantified against that in pokeweed mitogen (PWM) stimulated peripheral blood mononuclear cells. The expression of IL-6 in neoplastic B cells was confirmed by immunohistochemistry. We then looked for correlations between the amount of IL-6 concentrations. The amount of IL-6 mRNA correlated with the circulating IL-6 concentration, suggesting that the malignant cells were the source of IL-6 in these patients with B-cell NHL. Our results suggest that the circulating IL-6 in patients with B-cell NHL is derived from the neoplastic lymphoid cells, and that neoplastic cells may act as modulators of the general status of patients with B-cell NHL.

To study the involvement of cytotoxic granules in apoptosis of aplastic anaemia (AA), we analysed bone marrow clot sections of AA for apoptosis and perforin, granzyme B and T-cell intracellular antigen-1 (TIA-1) expression. Perforin, TIA-1 expression and apoptosis were significantly increased in AA patients compared with control subjects, but granzyme B was not. TIA-1 was significantly correlated with apoptotic cells of AA. No correlation was found between perforin and apoptotic cells of AA. These results suggest that perforin and TIA-1 play a role in the pathogenesis of AA. TIA-1 is implicated as an effector in the apoptosis of AA.

In order to clarify the characteristics of granulosa cell tumors of the ovary, extracellular matrix components were investigated by immunohistochemical techniques. Twenty-three granulosa cell tumors (GCT; eight juvenile and 15 adult type) were studied in comparison with non-neoplastic granulosa cells of human ovaries. In all 23 cases of GCT, chondroitin 6-sulfate proteoglycan revealed with antibody 3B3 was characteristically observed in the extracellular matrix in the solid nest, as well as in microfollicles. In the juvenile cases, the extracellular matrix also contained large proteoglycan (PG) revealed with antibody 2B1. Macrofollicles as well as microfollicles contained PG chondroitin 6-sulfate side chains with a significant amount of chondroitin 4-sulfate. By biochemical analysis using high pressure liquid chromatography, it was also found that disaccharide composition of glycosaminoglycan fractions extracted from granulosa cell tumor tissues consisted mainly of 2-acetamide-2-deoxyl-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (delta Di-6S). The characteristic feature of granulosa cell tumors is the accumulation of chondroitin sulfate PG, especially chondroitin 6-sulfate PG, which may be synthesized by the tumor cells themselves. Immunohistochemical characterization of the extracellular matrix components (collagen, laminin, heparan sulfate PG, chondroitin 4-sulfate PG) was also studied in relation to chondroitin 6-sulfate PG localization.