Borderline ovarian tumours in Vaud, Switzerland: incidence, survival and second neoplasms.
Between 1976 and 1996, 176 borderline ovarian tumours were registered in the Cancer Registry of the Swiss canton of Vaud, corresponding to an age-adjusted incidence (world standard) of 2.7 in 100,000. Incidence rose from 1.7 per 100,000 during 1976-81 to 2.7 per 100,000 during 1987-91, and then levelled off; 58% of cases were serous and 41% mucinous. Relative survival was 94% at 10 years; 18 second neoplasms were observed, compared with 10.3 expected, and there was a significant excess of invasive ovarian cancers (four observed, including three synchronous, compared with 0.4 expected). (+info)
Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms?
OBJECTIVE: To determine whether the long-term behavior of cystic mucinous neoplasms of the pancreas could be predicted using a novel, precisely defined classification of benign mucinous cystadenomas, noninvasive proliferative cystic mucinous neoplasms, and invasive mucinous cystadenocarcinomas. The primary interest was to obtain long-term follow-up after complete resection to determine the recurrence rates based on this objective classification. BACKGROUND: Current understanding is that all cystic mucinous neoplasms of the pancreas are potentially malignant and that mucinous cystadenomas, when completely removed, are biologically benign. Cystadenocarcinomas are thought to be less aggressively malignant than ordinary ductal adenocarcinoma, but reported recurrence rates vary widely and are unpredictable. METHODS: All patients who underwent "curative" resection for cystic mucinous neoplasms at Mayo Clinic Rochester from 1940 to 1997 were identified. All available pathology slides, gross specimens, and clinical records were reviewed, eliminating patients with inadequate documentation. Neoplasms were reclassified as mucinous cystadenomas, noninvasive proliferative mucinous cystic neoplasms, or invasive cystadenocarcinomas based on specific histologic criteria. RESULTS: Of 84 patients (70 women, 14 men) with cystic mucinous neoplasms of the pancreas, 54 were classified as cystadenomas, 23 as noninvasive proliferative cystic mucinous neoplasms, and only 7 as cystadenocarcinomas. Recurrent disease developed in none of the 77 patients without invasion, but 5 of the 6 patients surviving resection for cystadenocarcinomas died of recurrent cystadenocarcinoma within 5 years. CONCLUSIONS: When the neoplasm is completely resected and subjected to adequate histopathologic examination based on these objective criteria, absence of tissue invasion predicts a curative operation and detailed follow-up may be unnecessary. In contrast, a histologic diagnosis of invasive cystadenocarcinoma portends a dismal prognosis, similar to that of typical ductal adenocarcinoma of the pancreas. (+info)
Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers.
Allelic deletions of multiple chromosome 17q loci in sporadic ovarian cancer of epithelial origin suggest that inactivation of tumor suppressor gene(s) in these regions may be important for ovarian tumorigenesis. To further define the pattern of allelic imbalance in epithelial ovarian tumors of different histologies, a PCR-based assay was used to assess loss of heterozygosity (LOH) of polymorphic markers representative of TP53, BRCA1, NME1 and GH1, and region 17q23-25. LOH was observed for at least one marker in 68% of malignant tumors (n=60) and in 18% tumors of borderline malignancy (n=11), but not in benign tumors (n=5). The highest frequency of LOH in malignant tumors (64%) was observed with D17S801 on 17q25. Ten of 39 malignant ovarian tumors displaying LOH of at least one 17q marker, displayed a LOH pattern enabling the determination of a minimal region of overlapping deletion defined by D17S795 and D17S801. One borderline tumor also displayed an interstitial LOH pattern that overlapped this 17q25 minimal region of deletion. The histologies of malignant tumors displaying a pattern indicative of interstitial 17q deletions were of the endometrioid, clear cell and mucinous epithelial types. As the minimal region of overlap defined by these tumors overlap regions deleted in malignant tumors of all histologic types, and in a tumor of borderline malignancy, the 17q25-tumor suppressor may be implicated in the development of all types of epithelial ovarian tumors. (+info)
Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma.
In the present study we examined the localization and overexpression of heat shock proteins (hsps), mainly hsp90, in pancreatic carcinoma tissue compared with control tissue (including chronic pancreatitis and normal pancreas tissue), with the aid of immunohistochemical staining, in situ hybridization and reverse transcriptase polymerase chain reaction. Hsp90 alpha mRNA was overexpressed more highly in pancreatic carcinoma than in the control tissue. The proliferating-cell-nuclear-antigen labeling index was also high in pancreatic carcinoma tissue compared with the other tissue. These findings suggest that the overexpression of hsp90 alpha mRNA in carcinomas may be correlated with cell proliferation. However, hsp90 beta was constitutively overexpressed almost equally in all groups of pancreatic tissue including pancreatic carcinoma, chronic pancreatitis and normal pancreas tissue. Immunohistochemical staining demonstrated a differentiation in the expression of hsp90 between histological types of pancreatic carcinoma. These findings suggest that hsp90 alpha is involved in carcinogenesis and that hsp90 beta is correlated to structural conformation. Hsp90 alpha and hsp90 beta seem to perform different functions in tissue containing malignant cells. P53, MDM2 and WAF1, that were cell-cycle-related oncogene product were more strongly expressed in the nuclei of the cancer cells of the cancer tissue. Especially, MDM2 was more strongly expressed in mucinous carcinoma and the mucin secreting tissues surrounding pancreatic carcinoma tissue. The expression of MDM2 protein might also be correlated to secretion systems during structural conformation and be correlated to hsp90 beta. (+info)
P73 gene expression in ovarian cancer tissues and cell lines.
Thep73 gene, a homology of p53, is a new candidate of imprinting and tumor suppressor gene. To investigate the role of p73 in ovarian cancer, we studied the allelic expression in 56 cases of ovarian cancer using StyI polymorphism analysis. We also examined p73 expression by semi-quantitative reverse transcription-PCR as well as by Western blot analysis and DNA methylation study of the CpG island in exon 1 in ovarian cancer tissues and cell lines. Loss of heterozygosity was found in 8.3% (2 of 24) of the cases. Biallelic expression was demonstrated in 91.7% (22 of 24) of the tumor samples, in 70.8% (17 of 24) of the normal samples, and in 1 ovarian cancer cell line. Imbalanced expression and monoallelic expression were found in three and two pairs of matched samples, respectively. Overexpression of p73 was found in advanced ovarian cancer rather than in early-stage disease or in borderline ovarian tumor. No significant difference was found in the p53 expression. Three cell lines with absent p73 protein expression and one tumor sample with monoallelic expression were methylated in the CpG island. Demethylation in SKOV3 cell line using 5-azacytidine can reactivate the expression of this gene in both the mRNA and the protein level. Our results indicated that p73 was not imprinted in most of the ovarian cancer and normal tissues, but it could be involved in the advanced ovarian cancer through overexpression. DNA methylation may contribute to the lack of p73 expression. (+info)
The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation.
Proteolysis mediated by matrix metalloproteinases (MMPs) and serine proteinases is associated with cancer invasion and metastasis. Activation of latent proMMPs, and especially the proforms of the type IV collagen degrading gelatinases A and B (proMMP-2 and proMMP-9), is thought to be a critical step in this process. We have recently found that human tumour-associated trypsin-2 is a potent activator of proMMP-9 and it also activates proMMP-2 in vitro. Trypsinogen, MMP-2, and MMP-9 are expressed in ovarian cancer. To elucidate the function of trypsin in vivo, we studied whether high concentrations of trypsinogen-1, trypsinogen-2, their alpha(1)-proteinase inhibitor (API) complexes, and tumour-associated trypsin inhibitor (TATI) are associated with proMMP-2 and proMMP-9 activation in ovarian tumour cyst fluids. Zymography and immunofluorometric analysis of 61 cyst fluids showed a significant association between high trypsin concentrations and the activation of MMP-9 (P = 0.003-0.05). In contrast, the trypsin concentrations were inversely associated with the activation of MMP-2 (P = 0.01-0.02). Immunohistochemical analysis of ovarian tumour tissue demonstrated expression of trypsinogen-2 and TATI in the secretory epithelium. MMP-2 was detected both in stromal and epithelial cells whereas MMP-9 was detected in neutrophils and macrophage-like cells in stromal and epithelial areas. These results suggest that trypsin may play a role in the regulation of the MMP-dependent proteolysis associated with invasion and metastasis of ovarian cancer. (+info)
Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human ovarian tumors and tumor-associated macrophages.
This study investigates whether and to what extent cyclooxygenase type-2 (COX-2) and inducible nitric oxide-synthase (iNOS), both known to have an immunosuppressive effect, are expressed in human ovarian tumors. Because COX-2 and iNOS can be expressed by activated macrophages, the presence of tumor-associated macrophages and the expression of COX-2 and iNOS by these tumor-associated macrophages were determined. The results obtained may provide insight into the function of COX-2 and iNOS expression by tumors. The expression of COX-2 and iNOS in tumor cells and macrophages was assessed in 18 malignant, 15 borderline, and 14 benign human ovarian tumors by immunohistochemical staining of frozen tissue sections. The intra- and peritumoral macrophages were stained using an anti-CD68 monoclonal antibody. Most of the malignant tumors (15 of 18), 10 of 15 borderline, and 9 of 14 benign tumors showed COX-2 expression in the epithelial cells, a result which indicates that COX-2 expression is not exclusive to malignancy. In addition, COX-2 staining was more intense in the epithelial cells of benign and borderline tumors than in malignant tumors. Weak iNOS staining was observed in 5 of 18 malignant, 4 of 15 borderline, and 5 of 14 benign tumors. The number of tumor-associated macrophages varied widely between the different tumors. The highest number of tumor-associated macrophages (> or =20/0.125 mm(2)) was observed in malignant tumors, whereas low to moderate intra- and peritumoral macrophage infiltration (5-20/0.125 mm(2)) was observed in the borderline and benign tumors. COX-2-positive tumor-associated macrophages were found in 3 of 18 malignant tumors, 7 of 15 borderline tumors, and 1 of 14 benign tumors. The number of COX-2-positive tumor-associated macrophages ranged from 3 to 30% of the total macrophage population. Some malignant (4 of 18), borderline (5 of 15), and benign (2 of 14) tumors contained iNOS-positive macrophages. Notable was that COX-2- and iNOS-positive macrophages were predominantly located in the tumor stroma, the regions between tumor and stroma, and in the lumina of the tumor when located in the tumor tissue. These data indicate that not only malignant but also borderline and benign ovarian tumors can exhibit increased levels of COX-2 and iNOS expression. In addition, a small proportion of the tumor-associated macrophages found in malignant, borderline, and benign tumors seems to be in an activated state, judged by their iNOS and COX-2 expression. This subpopulation of tumor-associated macrophages was invariably located in the tumor stroma or in the lumina of the tumor, specifically suggesting that macrophages outside the tumor can be tumor cytotoxic. (+info)
Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer.
Recently, some studies have shown that delayed scanning with (18)F-FDG PET may help to differentiate malignant from benign pancreatic lesions. However, no study has evaluated the relationship between temporal changes in (18)F-FDG uptake and expression of hexokinase or glucose transporter. METHODS: Twenty-one consecutive patients with pancreatic cancer were studied preoperatively by dual-phase (18)F-FDG PET, performed 1 and 2 h after injection of (18)F-FDG. The standardized uptake value (SUV) of the pancreatic cancer was determined, and the retention index (RI) (%) was calculated by subtracting the SUV at 1 h (SUV1) from the SUV at 2 h (SUV2) and dividing by SUV1. The percentages of cells strongly expressing hexokinase type-II (HK-II) and glucose transporter-1 (GLUT-1) were scored on a 5-point scale (1 = 0%-20%, 2 = 20%-40%, 3 = 40%-60%, 4 = 60%-80%, 5 = 80%-100%) by visual analysis of immunohistochemical staining of paraffin sections from the tumor specimens using anti-HK-II and anti-GLUT-1 antibody (HK-index and G-index, respectively). RESULTS: SUV2 (mean +/- SD, 5.7 +/- 2.6) was higher than SUV1 (5.1 +/- 2.1), with an RI of 8.5 +/- 11.0. Four cases of cancer, in which SUV2 showed a decline from SUV1, showed a low HK-index (1.8 +/- 1.1), whereas 4 cases with an RI of > or =20 and 13 cases with an intermediate RI (0-20) showed significantly higher HK-indices (4.3 +/- 0.7 and 3.1 +/- 1.5, respectively; P < 0.05). RI showed a positive correlation with HK-index, with an R(2) of 0.27 (P < 0.05), but no significant correlation with the G-index. SUV1 showed no relationship with the HK-index but showed a weak positive correlation with the G-index, with an R(2) of 0.05 (P = 0.055). CONCLUSION: These preliminary findings suggest that the RI obtained from dual-phase (18)F-FDG PET can predict HK-II expression and that the SUV (at 1 h) has a positive correlation with GLUT-1 expression but not with HK-II expression. (+info)