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PubMed2005

Polycystic ovary syndrome and gynecological cancers: is there a link?

Polycystic ovary syndrome [PCOS] is the most common endocrinopathy of women in reproductive age. An association between PCOS and type-1 endometrial cancer has often been reported in the literature. The prolonged anovulation with consequent continued secretion of estrogen unopposed by progesterone may enhance the development and growth of this malignancy, particularly in young women. Hypersecretion of luteinizing hormone [LH], chronic hyperinsulinemia and increased serum insulin-like growth factor [IGF]-I levels may represent risk factors for endometrial cancer. However, data available in the literature do not allow a meta-analysis to be carried out to calculate an estimate of the relative risk of endometrial cancer in women with PCOS. Anecdotal cases of low-grade endometrial stromal sarcoma and carcinosarcoma have been reported in association with prolonged unopposed estrogen stimulation, and in particular with PCOS. A few studies have addressed the possibility of an association between PCOS and epithelial ovarian cancer risk, and the results are conflicting but generally reassuring, and similarly the few available data appear to exclude a strong association between PCOS and breast cancer.

Breast Neoplasms↗
PubMed1992

Systemic and local carcinogenesis by directly acting N-nitroso compounds given to rats by intravesicular administration.

A number of directly acting carcinogenic N-nitroso compounds were administered to female F344 rats intravesically, to assess their ability to induce tumors locally in the urinary bladder and systemically following absorption through the bladder mucosa. The compounds were alkylnitosoureas and alkylnitrosocarbamates and could be formed by interaction of amides with bacterially produced nitrite in infected bladders. Methylnitrosourethane was very toxic: doses of 1-2 mg caused death of some rats. A total dose of 0.15 mmol of ethylnitrosourethane, which was much less toxic, was administered to each rat and almost all developed bladder tumors. Ethylnitrosourea also gave rise to bladder tumors following intravesical treatment, and induced some tumors systemically, whereas methylnitrosourea, 2-methoxyethylnitrosourea and 2-hydroxypropylnitrosourea induced bladder tumors in high incidence and few tumors systemically. Nitrosooxazolidone was quite toxic and induced few bladder tumors. The dialkylnitrosoureas were more stable and some induced more tumors systemically than the monoalkylnitrosoureas. 1,3-Dimethylnitrosourea induced no bladder tumors and 1,3-diethylnitrosourea very few, but both induced tumors systemically that were similar to those induced by gavage treatment of rats. 1-Ethyl-1-nitroso-3-hydroxyethylurea, 1-hydroxyethyl-1-nitroso-3-ethylurea and 1-(2-hydroxypropyl)-1-nitroso-3-(2-chloroethyl)-urea induced bladder tumors in a majority of rats treated intravesically; the first induced many tumors systemically. Most of the bladder tumors were transitional cell papillomas and carcinomas, but there were a few squamous cell tumors, smooth muscle tumors, sarcomas and carcinosarcomas. The effects of intravesical administration of the directly acting alkylating compounds are compared with the effects of similar doses given to rats by gavage.

Administration, Intravesical↗
PubMed1984

Pleomorphic carcinoma of the gallbladder: case report and ultrastructural study.

Carcinomas of the gallbladder with pleomorphic spindle cell histology are unusual. We report such an occurrence in a 47-year-old male with a neoplasm showing both a mixed squamous and a pleomorphic spindle cell pattern. Ultrastructural studies supported the likelihood that this lesion represented a pleomorphic carcinoma and revealed unique paracrystalline structures intimately associated with tonofilaments. For this reason we believe that this and some other previously diagnosed sarcomas and carcinosarcomas of the gallbladder are in reality poorly differentiated carcinomas of either adeno, squamous, or mixed type. This illustrates the need for critical ultrastructural assay to determine the nature of poorly defined and differentiated neoplastic growths.

Carcinoma↗
PubMedDate not supplied

Selected ultrastructural aspects of urothelial and prostatic tumors.

Ultrastructural techniques have been widely applied in the study of urothelial and prostatic tumors. In the common proliferative diseases affecting the lower urogenital tract, electron microscopy has provided us with a greater understanding of the pathobiology and morphology of these disease processes. Specific diagnostic application, however, has been limited. In the unusual tumors affecting urothelium and prostate such as neuroendocrine carcinoma, carcinosarcoma, and sarcomas, electron microscopy has provided some practical diagnostic information of value in patient management. This paper provides a survey of the fundamental and practical contributions of ultrastructural studies in the prostatic and urothelial areas.

Adenocarcinoma↗
PubMed1980

Metabolism, antitumor activity, and acute toxicity of 5-fluoro-1,3-bis(tetrahydro-2-furanyl)-2,4-pyrimidinedione by oral administration to animals.

The metabolism, antitumor activity, and acute toxicity of 5-fluoro-1,3-bis-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FD-1) were investigated in animals, compared with 5-fluoro-1-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FT). It was found that after oral administration of FD-1, the level of 5-fluorouracil (5-FU) was maintained higher and longer than after administration of FT, and that a large amount of 5-FU was released from FD-1 by liver microsomal drug-metabolizing enzymes or spontaneous hydrolysis via 5-fluoro-3-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (3-FT) and FT. FD-1 had a significant activity against the solid form of Ehrlich carcinoma, sarcoma-180, hepatoma AH130, Yoshida sarcoma, Walker carcinosarcoma-256, and leukemia L1210 and P388, but not the ascitic forms, and it produced greater inhibition of tumor growth than FT. The acute toxicity of FD-1 was less than that of FT.

Administration, Oral↗
PubMed2003

Evaluation of the relationship between adenosarcoma and carcinosarcoma and a hypothesis of the histogenesis of uterine sarcomas.

The terminology of uterine sarcomas is confusing and has been inconsistently applied. The relationships among the various types of uterine sarcomas are unknown. To elucidate the relationship between carcinosarcoma (malignant mullerian mixed tumor) and adenosarcoma, a series of 26 consecutive endometrial carcinosarcomas was evaluated for the presence of an adenosarcoma-like component. Four of 26 carcinosarcomas (15%) had an adenosarcoma-like component. The clinical and pathologic features of these tumors were otherwise similar to ordinary endometrial carcinosarcomas. A histogenetic schema for uterine sarcomas is proposed, interrelating endometrial stromal sarcomas, adenosarcomas with and without sarcomatous overgrowth, and poorly differentiated sarcoma not otherwise specified. Although most carcinosarcomas are accepted as being metaplastic or sarcomatoid carcinomas, it is suggested that the carcinomatous component of 8% to 16% of carcinosarcomas arise within, or in the endometrium adjacent to, an adenosarcoma. This latter group is then integrated into the histogenetic schema. Observations based on our data and the limited data in the literature that support this hypothesis include: 13% of endometrial carcinosarcomas have gross and microscopic features of collision tumors, 13% have an adenosarcoma-like component, 16% have a low-grade stroma, and approximately 8% are biclonal indicative of a collision tumor. The most parsimonious interpretation of these data indicates that approximately 8% to 16% of endometrial carcinosarcomas arise because of malignant transformation of the epithelial component within, or in the endometrium adjacent to an adenosarcoma.

Adenosarcoma↗
PubMed1990

Immunohistochemical study of high-grade endometrial stromal sarcoma. An autopsy report in comparison with carcinosarcoma, leiomyosarcoma and normal endometrium.

An autopsy case of high-grade endometrial stromal sarcoma (ESS) is reported. Immunohistochemical study of the ESS was done in comparison with carcinosarcoma (CS), leiomyosarcoma (LMS) and normal endometrium in the uterus in order to trace the origin of ESS, which is a point of some controversy. Co-expression of keratin and vimentin and/or desmin positivity in several elements of CS and LMS, and glandular or stromal tissues in normal endometrium made it difficult immunohistochemically to be certain of the origin of ESS.

Antigens↗
PubMed1993

Different types and different prognosis-study of 310 uterine sarcomas.

Three hundred and ten cases of uterine sarcomas, among them, according to pathology: LMS (Leiomyosarcoma)--117, MMS (Mixed mesodermal sarcoma)--62, ESS (Endometrial stromal sarcoma)--56, CS (Carcinosarcoma)--27, RBMS (Rhabdomyosarcoma)--18 and other sarcomas--30, were retrospectively evaluated at the Maria Skłodowska-Curie Memorial Cancer Center between 1950 and 1985. These mesodermal tumors were divided into uterine corpus sarcomas (295) and the rarely occurring uterine cervix sarcomas. As the main modality of treatment 307 patients underwent surgery. Almost all patients received adjuvant radiotherapy but 51 cases of LMS. Overall 5-year survival was 34.5% and in particular subgroups the survivals were as follows: the best, 52% in LMS; lower, 30% in ESS; poor survival about 20% in CS and MMS. In spite of low curability in the majority of subgroups except LMS, the cases of CS with primary site in uterine cervix distinguished itself with better results. No significant survival advantage was found for surgery plus radiotherapy in LMS with low grade mitotic activity, (10 mitoses/10 HPF) compared with surgery alone (63% and 54%). These cases seem to have better prognosis in LMS with high grade mitotic activity (10 mitoses/10 HPF) and do not require adjuvant radiotherapy.

Adult↗
PubMed2001

Positron emission tomography with (18)F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging.

OBJECTIVE: The effectiveness of positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) for diagnosis of uterine sarcoma was evaluated in comparison to the effectiveness of magnetic resonance (MR) imaging and power Doppler imaging. METHOD: The cases of five Osaka City University Hospital patients diagnosed with uterine sarcoma based on histopathological examination, in whom FDG-PET, MR imaging, and power Doppler imaging studies had been performed preoperatively, were reviewed. A comparative study of the usefulness of these three imaging modalities for diagnosis of sarcoma was conducted. Tumors comprised three leiomyosarcomas, one endometrial stromal sarcoma, and one carcinosarcoma. RESULTS: FDG-PET examinations were 100% positive for the five sarcomas; MR imagings were 80% positive (four of five cases), and US was 40% positive (two of five cases). The mean standardized uptake value of the sarcomas was 4.5 +/- 1.3. CONCLUSION: The sarcoma lesions were clearly imaged by FDG-PET. FDG-PET may be a most useful diagnostic method for uterine sarcoma.

Aged↗
PubMed2004

Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A retrospective study of 31 cases.

AIMS: To assess the usefulness of immunohistochemistry in delineating tumour diagnoses on a series of morphologically diagnosed renal spindle cell tumours (RSCTs). METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues from 31 morphologically diagnosed tumours were reinterpreted in light of newly obtained immunohistochemical information. By morphology, six had originally been classified as sarcomatoid carcinoma, five as spindle cell tumour (NOS), four as sarcoma (NOS), three as leiomyoma, three as leiomyosarcoma, and one each as fibrous polyp, hamartoma, neurilemmoma, mesoblastic nephroma, medullary fibroma, angiomyolipoma, haemangiopericytoma, malignant rhabdoid tumour, malignant Triton tumour, and carcinosarcoma. The application of immunohistochemistry verified the original diagnosis in 18 cases (18/31, 58%), confirming the diagnosis of sarcomatoid renal carcinoma (4/6), leiomyoma (2/3), leiomyosarcoma (3/3), sarcoma (NOS) (2/4), carcinosarcoma (1/1), malignant rhabdoid tumour (1/1), malignant Triton tumour (1/1), fibrous polyp (1/1), mesoblastic nephroma (1/1), hamartoma (1/1), and angiomyolipoma (1/1). Different tumour designations were suggested in 13 cases (13/31, 42%), including carcinosarcoma, sarcoma (NOS), leiomyosarcoma, solitary fibrous tumour, monomorphic/biphasic angiomyolipoma, endometrial stromal tumour, and congenital mesoblastic nephroma. CONCLUSIONS: Our data indicate that although morphology is most important in formulating the initial differential diagnosis, the addition of immunohistochemistry is vital in arriving at the correct classification of RSCTs.

Adolescent↗
PubMed1987

Vimentin: an evaluation of its role as a tumour marker.

In this study we examined 198 sarcomas, 38 carcinomas, 13 'tumours with a spindle cell component' and 22 malignant melanomas with a commercial monoclonal vimentin antibody. All histopathological material was formalin fixed and paraffin embedded. The results show this antibody to be a sensitive and specific marker of mesenchymal derivation or differentiation. It is a useful tool in separating sarcomas from most carcinomas, and in separating malignant melanomas from carcinomas. When used in combination with a cytokeratin antibody it identifies carcinosarcomas and synovial sarcomas.

Antibodies, Monoclonal↗
PubMed1997

[Uterine sarcoma treated by surgery and postoperative radiation therapy. Patterns of relapse, prognostic factors and role of radiation therapy].

The objective was to evaluate the results of a combination of surgery and postoperative radiotherapy in patients with uterine sarcoma, to describe the patterns of relapse and to define prognostic factors. From 1980 to 1993, 29 patients (median age: 56 years) presenting with uterine sarcoma have been treated with surgery and postoperative irradiation. The histology was: leiomyosarcoma: 11; carcinosarcoma: 12; stromal sarcoma: 6. The distribution by stage was: pT1: 18; pT2: 5; pT3: 3; pT4: 3; pNO: 27; pN1: 2. Gross residual disease was present in 4 patients. External beam irradiation was performed in all the cases and brachytherapy in 19. Chemotherapy was given in 3 patients. The overall survival rate was 66% at 2 years and 57% at 5 years with a disease free survival of 54% at 2 years and 50% at 5 years. Seven patients relapsed locally and 8 developed metastases. One patient died of ileitis. In a multivariate analysis, the disease free survival was strongly influenced by the menopausal status. The survival in this study is higher than that described in series of patients treated with surgery alone. This study confirms the worse prognosis of uterine sarcoma in postmenopausal women.

Adult↗
PubMed2004

Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999.

OBJECTIVES: To determine the association of race with incidence, histology, treatment, and survival in women with uterine sarcoma during the period 1989-1999. METHODS: Uterine sarcomas were defined as leiomyosarcoma, carcinosarcoma, high-grade endometrial stromal sarcoma (HGESS), adenosarcoma, and sarcoma not otherwise specified (NOS). We used cases from Surveillance, Epidemiology, and End Results (SEER) program to compare uterine sarcoma among women >35 years of age. Using data from 1989 to 1999, we compared race-specific age-adjusted incidences, histological distributions, extent of disease at diagnosis, and race-specific survival. RESULTS: During the period of 1989-1999, 2677 women were diagnosed with uterine sarcoma, 2098 (78%) of whom were white and 420 (16%) of whom were black, and 159 (6%) of whom were of other races. The overall age-adjusted incidence for blacks was twice that of whites and more than twice that of women of other races (7/10(5) vs. 3.6/10(5) vs. 2.7/10(5), P < 0.0001). Racial differences in the incidence of uterine sarcoma existed for leiomyosarcoma (1.51/10(5) for blacks vs. 0.91/10(5) for whites, and 0.89 for women of other races, P < 0.01) and carcinosarcoma (4.3/10(5) for blacks, vs. 1.7/10(5) for whites, and 0.99 for women of other races, P < 0.001), but not for other histological types. Blacks with stage II disease were less likely to receive radiation in addition to surgery compared to whites (33% vs. 54%, P < 0.05). Five-year relative survival of patients with disease beyond the uterus was significantly longer for those that received radiation and surgery compared to those that received surgery alone. There were no racial differences in survival for women that received similar therapy. CONCLUSIONS: Adjuvant therapy improved survival for women with stage II-IV disease. Survival of black and white patients who received comparable treatment was similar.

Adult↗
PubMed1986

Carcinosarcoma of the colon. Report of a unique case with light and immunohistochemical studies.

A unique case of carcinosarcoma of the colon is reported. The tumor invaded the bowel wall deeply, metastasized widely, resisted multi-agent chemotherapy, and caused the patient's death 4 years later. The tumor was composed of adenosquamous carcinoma admixed with sarcoma showing osseous, cartilaginous, and nonspecific spindle-cell differentiation. Although carcinoembryonic antigen appeared limited to carcinoma cells, cytokeratin immunoreactivity was observed in both carcinoma and sarcoma cells. Like carcinosarcomas at other body sites, the finding of cytokeratin in sarcoma cells supports partial epithelial differentiation in this component, likely retained from carcinoma precursor cells.

Aged↗
PubMed2006

PDGFR-alpha as a potential therapeutic target in uterine sarcomas.

OBJECTIVE: Uterine sarcomas are a heterogeneous group of tumors with a propensity for metastasis and resistance to conventional therapy. Recent success in the treatment of other solid tumors with the targeted tyrosine kinase inhibitor imatinib mesylate offers new avenues for investigation. The primary target of imatinib is c-kit, but the drug also inhibits PDGFR-alpha and PDGFR-beta. Given the lack of identified molecular targets in endometrial stromal sarcomas, leiomyosarcomas, and carcinosarcomas, the purpose of this study was to determine the protein expression of c-kit, PDGFR-alpha, and PDGFR-beta in these tumors as a preliminary step to determining their susceptibility to directed therapy. A secondary goal was to identify specific gene mutations that might be associated with activation of these proteins in uterine sarcomas. METHODS: Archived tissue from 42 cases of uterine sarcomas was stained for c-kit, PDGFR-alpha, and PDGFR-beta using immunohistochemistry. Laser-capture microdissected samples of uterine carcinosarcomas, or homogeneous areas of leiomyosarcomas or endometrial stromal sarcomas, were subjected to genetic analysis of PDGFR-alpha exons 12 and 18. RESULTS: The majority (38/42, 90%) of uterine sarcomas lacked c-kit expression and 90% (38/42) demonstrated negative or weak staining for PDGFR-beta. In contrast, 70% (30/42) of cases had strong staining for PDGFR-alpha in the tumor but not in normal myometrium or endometrium. Sequencing results revealed no mutations in exons 12 or 18 of PDGFR-alpha. CONCLUSION: c-kit and PDGFR-beta are unlikely to represent primary treatment targets in uterine sarcomas. The strong expression of PDGFR-alpha in uterine sarcoma specimens suggests a role for this receptor in tumor development, although its potential as a therapeutic target requires further investigation.

Female↗
PubMed1994

Establishment of a new lung sarcoma cell line from a human lung carcinosarcoma.

A cell-line (UACC 2561), was established from a biopsy specimen of a lung carcinosarcoma. The patient had Stage III non-small cell lung cancer. Characterization of this cell line revealed highly aneuploid cells containing multiple clonal chromosome alterations with growth in nude mice within 3 weeks following subcutaneous injection. The cell line UACC 2561 stained positive for vimentin and displayed resistance to a variety of chemotherapeutic agents. Polymerase chain reaction followed by single-strand conformational polymorphism analysis revealed the presence of a K-ras 12 codon mutation. This mutation was confirmed by mutation specific PCR analysis for mutant K-ras alleles and direct DNA sequencing to be a GGT to GTT at codon 12 of the K-ras gene. Examination by PCR-SSCP for p53 mutations did not reveal any point mutations in exon 5-8 of the p53 gene. This relatively rare cell line may represent a useful model to investigate human lung sarcomas.

Animals↗