PubMed Health⌕ Search

Biomedical subjects

M L Carcangiu

Publications and source records attributed to M L Carcangiu.

At least 19 recordsLinked to original sources
PubMed1998

CA 125 may not reflect disease status in patients with uterine serous carcinoma.

BACKGROUND: Although CA 125 level correlates with response to therapy in patients with serous carcinoma of the ovary, the utility of CA 125 in patients with high risk or metastatic endometrial carcinoma has not been established. METHODS: CA 125 was tested as a marker of disease status in patients with endometrial serous carcinoma (SC) undergoing adjuvant chemotherapy. All patients received monthly intravenous chemotherapy with cisplatin, cyclophosphamide, and doxorubicin at standard doses (median number of courses, 6; range, 2-8 courses). Serum CA 125 was measured at diagnosis and before each course. After the completion of chemotherapy, patients were examined every 3 months and the CA 125 level was measured. RESULTS: A total of 220 serum specimens from 15 patients with invasive SC were analyzed. All five patients who died of disease had clinical or radiographic evidence of tumor, which CA 125 elevation did not precede or predict. One patient with advanced disease at staging never had an elevated CA 125 level but died of disseminated disease 14 months after diagnosis. At last follow-up, 3 patients who were without evidence of disease > 36 months from diagnosis had significant false-positive elevations in their CA 125 level (>50 u/mL) lasting 1, 2, and 4 months, respectively, during therapy. The sensitivity for advanced disease was only 57% at presentation. CONCLUSIONS: CA 125 may reflect advanced stage disease and portend a poor prognosis, but may not add information to that gained by history and physical examination, preoperative studies, or surgery that already is mandated by this high risk histology. This circulating marker appears to have limited utility in monitoring the effects of adjuvant therapy for SC, and may not predict recurrence in the absence of other clinical findings.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes.

Malignant tumors of the thyroid gland vary considerably in aggressiveness, ranging from a well-differentiated, clinically indolent, to an undifferentiated, often lethal phenotype. Undifferentiated (anaplastic) thyroid tumors are supposed to be derived, through a process of progression, from previously differentiated neoplasms. A common genetic alteration in thyroid tumors is the rearrangement of the tyrosine kinase-encoding RET proto-oncogene, leading to the generation of chimeric RET/PTC oncogenes. To define the characteristics of the thyroid tumor subset with RET rearrangements, we have investigated its activation by a combined immunohistochemistry and reverse transcription-PCR approach in a series of 316 well-characterized thyroid tumors representative of the main diagnostic groups. RET activation was detected in 81 of 201 (40.3%) papillary carcinomas. It correlated with tumors exhibiting the "classic" morphological features of papillary cancer or with the microcarcinoma subtype (P = 0.017). RET activation in papillary carcinoma was not associated with clinical markers (such as large tumor size, extrathyroidal extension, or metastases) of increased morbidity. Follicular-type neoplasms (61 adenomas and 22 carcinomas), as well as the aggressive poorly differentiated (15 cases) or undifferentiated (anaplastic) carcinomas (17 cases), were negative. This study demonstrates that all thyroid carcinomas harboring activating RET rearrangements exhibit a well-differentiated phenotype, that of papillary carcinoma, and indicates that the subset of RET/PTC-positive papillary carcinomas do not progress to more aggressive, less differentiated tumor phenotypes.

Adolescent↗
PubMed1997

Expression of plasminogen activator inhibitor-2 in epithelial ovarian cancer: a favorable prognostic factor related to the actions of CSF-1.

In ovarian cancer cells, the macrophage colony-stimulating factor-1 (CSF-1) induces the release of plasminogen activator inhibitor-2 (PAI-2), and high levels of PAI-2 as well as of CSF-1 in ovarian cancer ascites are independently correlated with poor outcome. We now study the effect of CSF-1 on PAI-2 expression in vitro and the significance of cellular PAI-2 expression in vivo. Immunohistochemical detection of PAI-2 was studied in primary and metastatic tissues from 130 epithelial ovarian cancer cases. Kaplan-Meier curves of survival were compared with the results of log-rank test. The Cox regression model was used for multivariate analysis. The effect of CSF-1 on PAI-2 expression in ovarian cancer cells was also examined in vitro. Fifty-eight percent of the primary tumors and 68% of the metastases expressed PAI-2. PAI-2 expression in the metastases of invasive stages III and IV cases was strongly predictive of a prolonged disease-free and overall survival. This finding was associated with low residual disease and was also an independent factor for disease-free survival. In vitro, CSF-1 treatment of ovarian cancer cells resulted in a decrease in cellular staining for PAI-2 while increasing the release of PAI-2 into the conditioned medium. In vivo, we also found an inverse correlation between expression of CSF-1 and that of PAI-2 in the primary tumors. We thus describe the favorable independent prognosis of cellular PAI-2 expression in the metastases of ovarian cancer. Moreover, an inverse correlation was observed between CSF-1 and PAI-2 expression in vivo. This lends support for a primary role of cell-surface (vs. secreted)-mediated events of plasminogen activation in the development of invasive, poor prognostic phenotypes.

Epithelium↗
PubMed1997

Abnormal intracellular and extracellular distribution of basement membrane material in papillary carcinoma and hyalinizing trabecular tumors of the thyroid: implication for deregulation of secretory pathways.

Papillary carcinoma (PC) and hyalinizing trabecular tumors (HTT) of the thyroid share several morphological features, including the presence of nuclear pseudoinclusions (NPI). One of the distinct characteristics of HTT is its hyalinizing stroma, which contains abundant basement membrane (BM) material. We investigated the distribution of BM material in PC and HTT. Fifteen cases of PC and nine cases of HTT were analyzed immunohistochemically with monoclonal antibodies for type IV collagen and laminin. Three stromal staining patterns were observed: (1) linear staining along the epithelium lining papillae, between trabeculae, and around follicles; (2) focal absence of staining; (3) lumpy or diffuse stromal staining. Although the latter was more commonly seen in HTT, all three patterns were present in both tumor types. More interestingly, we observed two hitherto undescribed intracellular staining patterns in both tumor types: intracytoplasmic dotlike staining and staining of NPI. Electron microscopy was performed in three cases of PC. Dilated cisternae of endoplasmic reticulum containing dense amorphous material resembling BM were observed in the cytoplasm in one case and in the NPI in another. These findings suggest the presence of a common pathway for the abnormal production of BM in both PC and HTT. Two mechanisms that may account for the abnormal intracellular detection of BM materials are proposed: (1) intracellular invagination/phagocytosis of extracellular matrix by the tumor cells; (2) abnormal production or alteration in secretory pathway in tumor cells resulting in intracellular accumulation and intranuclear invagination. The combination of immunohistochemical and electron microscopic findings favors the latter. The similar patterns of BM deposition shared by PC and HTT further support the hypothesis that PC and HTT are related to each other.

Basement Membrane↗
PubMed1997

Endometrioid endometrial adenocarcinoma with psammoma bodies.

Since the wide acceptance of serous carcinoma as a distinct subtype of endometrial carcinoma, almost all endometrial carcinomas with psammoma bodies have been classified as such. We describe eight cases of endometrioid endometrial adenocarcinoma with psammoma bodies and discuss their clinicopathologic features. The patients ranged in age from 37 to 79 years. Psammoma bodies were present in the curettage material in three and in the hysterectomy specimens in all cases. The tumors were well to moderately differentiated with at least focal squamous metaplasia. Four of eight cases also showed a focal villoglandular architecture. Inflammation and necrosis were present in all cases, and four had features of pyometra. Deep myometrial invasion was present in six cases. Diffuse lymphatic invasion was present in six, and one showed perivascular lymphocytic infiltrate in the absence of myometrial invasion. The tumors metastasized to lymph nodes in four of eight cases. One case showed intranodal psammoma bodies in the absence of endosalpingiosis or tumor. Intra-abdominal recurrence was present in only one case and was endometrioid with rare psammoma bodies. All patients are alive, six with no evidence of disease, one with stable periaortic lymphadenopathy, and one with progressive disease. This report suggests that endometrioid endometrial carcinoma may rarely be associated with psammoma bodies, the formation of which is most likely due to inflammation and necrosis. It also suggests that endometrioid carcinoma with psammoma bodies has a higher surgical stage and is more likely to have lymphatic invasion and lymph-node metastases and hence require surgical staging. The pattern of spread appears to be different from uterine papillary serous carcinoma, and the rate of survival is similar to stage-matched endometrioid carcinoma without psammoma bodies.

Adenocarcinoma↗
PubMed1997

Stage IA uterine serous carcinoma: a study of 13 cases.

Although in endometrioid type endometrial carcinoma depth of invasion is a powerful predictor of extrauterine disease and survival, in serous carcinoma its importance is unclear. Recurrences and death in patients with serous tumors confined to the endometrium or an endometrial polyp have been reported. In other studies, however, the absence of myometrial invasion was correlated with a more favorable course. In an attempt to clarify this issue, we reviewed 13 completely staged, stage IA serous carcinomas with follow-up from 10 to 93 months (median 38), in which extensive histologic examination had been performed. Serous carcinoma was identified in an endometrial polyp in six cases, in an endometrial polyp and associated endometrium in four, and solely in the endometrium in three cases. No other histologic types of endometrial carcinoma were present, and there was no myometrial invasion. Multifocal serous intraepithelial carcinoma was also seen in 12 cases. Two of the patients died of disease with intraabdominal carcinomatosis at 10 and 14 months after presentation. The overall estimated survival was 83%, showing a relatively favorable prognosis. In conclusion, although the absence of histologically detected myometrial invasion may be associated with recurrences and death in serous carcinoma, an accurately assessed stage based on a careful histologic examination appears to be, at present, the most reliable predictor of survival.

Aged↗
PubMed1997

Uterine pathology in tamoxifen-treated patients with breast cancer.

In the last 20 years, tamoxifen has become the drug of choice in the treatment of breast carcinoma in both advanced and early stages. Furthermore, the ability of tamoxifen to prevent mammary carcinoma in the contralateral breast has prompted the creation of trials that include healthy patients with an increased risk of developing breast cancer with the purpose of verifying the drug's prophylactic action. As a consequence, a large number of healthy women or women with a long life expectancy are being treated with tamoxifen for long periods, making it crucial to study the possible long-term effects associated with this therapy. A weak estrogen-like effect of tamoxifen on the endometrium has been documented. This is supported by the increased incidence of glandular hyperplasia, polyps, carcinoma, and sarcoma in tamoxifen-treated patients. Some studies have shown that not all endometrial carcinomas arising in tamoxifen-treated patients have the favorable histologic and prognostic features typical of estrogen-associated endometrial cancers. This, in conjunction with the demonstrated carcinogenicity of tamoxifen in some animal models, indicates the need for caution in the use of this drug and makes strict gynecologic surveillance of tamoxifen-treated patients imperative.

Antineoplastic Agents, Hormonal↗
PubMed1996

Epithelial expression and chromosomal location of human TLE genes: implications for notch signaling and neoplasia.

The TLE genes are the human homologues of Drosophila groucho, a member of the Notch signaling pathway. This pathway controls a number of different cell-fate choices in invertebrates and vertebrates. We are interested in investigating the functions of the TLE gene family during epithelial determination and carcinogenesis. We show that expression of individual TLE genes correlates with immature epithelial cells that are progressing toward their terminally differentiated state, suggesting a role during epithelial differentiation. In both normal tissues and conditions resulting from incorrect or incomplete maturation events, such as metaplastic and neoplastic transformations, TLE expression is elevated and coincides with Notch expression, implicating these molecules in the maintenance of the undifferentiated state in epithelial cells. We also show that TLE1 and TLE2 are organized in a tandem array at chromosomal location 19p13.3, while TLE3 maps to 15q22.

Animals↗
PubMed1996

Malignant uterine smooth muscle tumors: role of etoposide, cisplatin, and doxorubicin (EPA) chemotherapy.

BACKGROUND: Nearly 80% of patients with malignant uterine smooth muscle tumor will suffer local relapse and/or distant metastases after initial surgical resection. There is no convincing evidence that the addition of pelvic radiation improves the outcome. However, adjuvant chemotherapy might be an appropriate therapeutic modality. METHODS: Between 1986 and 1991, 13 consecutive patients with malignant uterine smooth muscle tumors were treated at Yale-New Haven Hospital with a combination chemotherapy containing etoposide 100 mg/M2 on days 1 and 2, cisplatin 50 mg/M2 on day 1, and doxorubicin 50 mg/M2 on day 1, repeated every 28 days. Six patients had Stage I disease, one patient had Stage III disease, and six patients had Stage IV disease. The number of cycles ranged from 2 to 9. RESULTS: The median follow-up was 30 months (range 4-81). The mean overall survival for the group was 43.1 +/- 6.7 months, with the progression-free interval of 25.5 +/- 8.0 months. Of the seven patients with evaluable disease, one patient had complete response and one had partial response (total response rate of 28.6%). Of the six patients treated adjuvantly, three recurred at 9, 33, and 59 months (recurrence rate of 50%). CONCLUSIONS: We conclude that this combination has only modest activity against malignant uterine smooth muscle tumors at the schedule and doses tested.

Adult↗
PubMed1996

Uterine papillary serous carcinoma treated with intraperitoneal cisplatin and intravenous doxorubicin and cyclophosphamide.

This study was designed to evaluate the efficacy of intraperitoneal cisplatin and intravenous doxorubicin and cyclophosphamide in patients with uterine papillary serous carcinoma. Sixteen patients with uterine papillary serous carcinoma underwent complete surgical staging and placement of an intraperitoneal port. Postoperatively, they received cisplatin (100 mg/m2) given intraperitoneally and doxorubicin (50 mg/m2) intravenously and cyclophosphamide (600 mg/m2) intravenously every 4 weeks for 6 cycles. The intraperitoneal ports did not function in 3 patients immediately following surgery. The remaining 13 patients constitute the study group. The patients ranged in age from 37 to 77 years. There were 1 patient with Stage IA, 3 with Stage IB, 2 with Stage IIB, 2 with Stage IIIA, 2 with Stage IIIC, 1 with Stage IVA, and 2 with Stage IVB. At the end of surgery no gross residual disease remained except for 1 patient who had less than 1-cm nodules in the peritoneal cavity. Eleven of the patients underwent 6 cycles of chemotherapy, 1 patient underwent 3 cycles, and 1 patient underwent 1 cycle. A total of 71 cycles of chemotherapy were given. All patients developed alopecia. Two patients developed neutropenic fever, one was treated with antibiotics, the other patient died from urosepsis. One patient had a > 15% decrease in left ventricular ejection fraction which led to a dose reduction of doxorubicin. One patient had a urinary tract infection and one patient developed a port infection which necessitated its removal. Seven patients have died, 1 is alive with disease, and 5 patients are alive with no evidence of disease. Five of the 7 patients with extrauterine disease have died of disease. One is alive with disease and the other is free of disease. The media survival of these patients was 34 months with an overall 3 years survival of only 24.1%. Although the protocol was reasonably well tolerated, the overall survival did not differ from that of a similar group of patients treated at our institution with intravenous chemotherapy. There was a high incidence of dysfunction of the intraperitoneal ports (25%). This approach with intraperitoneal cisplatin presents no therapeutic advantage for these patients.

Adult↗
PubMed1996

Combination chemotherapy with etoposide, cisplatin, and doxorubicin in mixed müllerian tumors of the adnexa.

Eleven patients with ovarian (9) or fallopian tube (2) mixed müllerian tumors who underwent primary surgery at Yale New Haven Medical Center between 1986 and 1994 were treated with etoposide, cisplatin, and doxorubicin. Responses were observed in three (60%) of five evaluable patients with two complete (40%) and one partial (20%) response. Median survival time was 17 months with an estimated 3-year survival of 18%. Survival may have been improved with earlier stage disease, but survival was not significantly improved with optimal surgical cytoreduction in patients with advanced disease. Four patients required dose reductions for myelosuppression and there was one treatment related death. Toxicity was comparable to other combination chemotherapy regimens. EPA has modest therapeutic activity in ovarian and fallopian tube MMT.

Aged↗
PubMed1995

Genetic analysis of benign, low-grade, and high-grade ovarian tumors.

Genetic abnormalities were assessed in 56 benign, low-, and high-grade ovarian tumors using comparative genomic hybridization (CGH) and analysis of loss of heterozygosity (LOH). In addition, 95 epithelial tumors were analyzed for microsatellite repeat instability. DNA sequence copy number abnormalities (CNAs) were not detected in the benign tumors, and more were detected in high-grade than in low-grade cancers. Almost no microsatellite repeat instability was detected in these cancers. CNAs occurring in more than 30% of the cancers included increased copy number on 3q25-26 and 8q24 and reduced copy number on 16q and 17pter-q21. Another 14 CNAs occurred in more than 20% of the cancers. Increased copy number at 3q25-26 and 20q13 was the most frequent CNA in low-grade tumors, and increased copy number at 8q24 occurred preferentially in high-grade tumors. The presence of a large number of CNAs per tumor was significantly correlated with reduced patient survival duration. Reduced copy number on 17pter-q21 was most strongly associated with accumulation of a large number of CNAs. The overall concordance between LOH and reduced copy number detected by CGH was 84%, but only 31% of the LOH was associated with reduced copy number detected using CGH.

Chromosome Aberrations↗
PubMed1995

Alterations in Notch signaling in neoplastic lesions of the human cervix.

The development of cancer is a cellular process that reflects and is partly driven by alterations in cell determination. Mutations in various molecules responsible for cell determination have been identified as being oncogenic, but little is known about the involvement of normal cell fate-determining mechanisms in the oncogenic process. The Notch pathway defines an evolutionarily conserved, general cell interaction mechanism that controls fundamental aspects of cell determination during vertebrate and invertebrate development. We have explored the involvement of the human Notch pathway in human cervical tissues, which define a cellular environment where cell fate changes take place and where neoplastic conditions have been well characterized. Our evidence suggests that Notch expression is associated with cell populations that are undergoing cell fate changes and that Notch activity can be used to monitor cell fate abnormalities in cervical as well as other epithelial neoplasias.

Antibodies↗
PubMed1995

A phase II study of etoposide, cisplatin, and doxorubicin chemotherapy in mixed müllerian tumors (MMT) of the uterus.

Mixed Müllerian tumors (MMT) of the uterus are aggressive entities that result in a very poor prognosis even for patients in whom the disease is limited to the uterus. This phase II trial was undertaken in an attempt to improve overall survival as well as progression-free survival of these patients. Forty-two consecutive patients were treated with a combination chemotherapy containing etoposide 100 mg/m2 on Days 1 and 2, cisplatin 50 mg/m2 on Day 1, and doxorubicin 50 mg/m2 on Day 1, repeated every 28 days. There were 23 patients with early-stage disease (stages I and II) and 19 patients with advanced (stages III and IV) or recurrent disease. In the early-stage group, the number of cycles ranged from 2 to 9 (5.2 +/- 1.9). The median follow-up was 32 months (range 11-93). There were five recurrences: three patients died of disease at 11, 36, and 51 months, and two patients are still alive with disease at 12 and 19 months. Two-year overall survival was 92%. In the advanced disease group, the number of cycles ranged from 1 to 11 (5.9 +/- 2.4). The median follow-up for this group was 20 months (range 5-62). The median overall survival was 18 months. Two-year overall survival was 33%. Two-year progression-free survival was 20%. Four patients were evaluable for response. There were two complete responses (duration 15-33 months) and two partial responses (duration 6-10 months). The responders were patients whose adenocarcinoma component was of the papillary serous (UPSC) variety. The chemotherapy combination appears to be highly active in early-stage disease. In the advanced uterine MMT it has moderate activity, especially when associated with the UPSC component.

Aged↗
PubMed1995

Microsatellite instability in ovarian neoplasms.

Microsatellite instability has been observed in a variety of sporadic malignancies, but its existence in sporadic ovarian cancer has been the subject of conflicting reports. We have performed a polymerase chain reaction-based microsatellite analysis of DNAs extracted from the neoplastic and non-neoplastic tissues of 41 ovarian cancer patients. Tumour-associated alterations were observed in seven (17%) of these cases. Clinicopathological correlations revealed that: (1) alterations among tumours classified as serous adenocarcinomas occurred with relatively low frequency (2/24 or 8%); (2) most of the tumours with microsatellite alterations (5/7 or 71%) were of less common histopathological types (epithelial subtypes such as endometrioid and mixed serous and mucinous, or non-epithelial types such as malignant mixed Müllerian or germ cell tumours); (3) tumour-associated alterations were observed in 3/4 (75%) of the patients with stage I tumours vs 4/37 (11%) of the patients with stage II, III and IV tumours (P = 0.01); (4) tumour-associated microsatellite instability was found to occur with similar frequencies among patients with and without clinical features suggestive of familial disease, including positive family history, early onset, or multiple primary tumours. In summary, we have observed microsatellite alterations in the neoplastic tissues of ovarian cancer patients with diverse genetic backgrounds and clinicopathological features. The pattern of alterations is consistent with the possibility that multiple mechanisms may be responsible for microsatellite instability in ovarian neoplasms.

Adult↗
PubMed1995

Early pathologic stage clear cell carcinoma and uterine papillary serous carcinoma of the endometrium: comparison of clinicopathologic features and survival.

Clear cell carcinoma (CCC) and uterine papillary serous carcinoma (UPSC) are aggressive variants of endometrial carcinoma that may coexist or share some clinicopathologic features suggesting a similar biologic spectrum and the need for a common therapeutic approach. Twenty-nine cases of pathologic FIGO stage I and II CCC and 47 cases of FIGO stage I and II UPSC seen and treated at Yale-New Haven Hospital were reviewed, and the survival rates with regard to various pathological parameters were compared. Both groups of patients had similar clinical profiles with respect to presentation, age, weight, and medical problems. The 5-year survival for pathologic stage I patients with CCC was 72% and for those with UPSC 44%. The 5-year survival for pathologic stage II patients with CCC was 59% and for those with UPSC 32%. Analysis of survival showed that the depth of myometrial invasion, the presence of vascular space invasion, and the admixture of endometrioid features did not influence survival in either group of patients. In CCC, survival was also not influenced by the predominant histologic pattern, i.e., papillary versus nonpapillary. The results of this study suggest that early stage CCC and UPSC have similar clinicopathologic profiles, suggesting the need for aggressive approaches including a staging laparotomy and possibly similar therapy. However, the stage I CCC patients had a significantly better survival than the stage I UPSC patients.

Adenocarcinoma, Clear Cell↗
PubMed1995

Transformation of ovarian dysgerminoma to yolk sac tumor: evidence for a histogenetic continuum.

Dysgerminoma has traditionally been considered an end-stage neoplasm without potential for further differentiation. Although there have been several reports of transformation of testicular seminoma to yolk sac tumor, a similar event has not been previously reported in dysgerminoma of the ovary. Three cases of ovarian germ cell tumor (two pure dysgerminomas and one mixed germ cell tumor with dysgerminoma and yolk sac components) that revealed histologic changes compatible with early transformation to yolk sac tumor are described. In general, the areas of transformation were located at the periphery of the tumor lobules which otherwise had features of typical dysgerminoma. They were characterized by the presence of microcysts and small glandular structures, which though not readily identified on H&E became more evident with stains for keratins, alpha-fetoprotein, and blood group-related antigen. The small size and focal nature of change, and the apparent transition favor the interpretation that this change represents transformation rather than admixture of two germ cell components. The relationship of dysgerminoma to the solid variant of yolk sac tumor is discussed and an alternate histogenetic scheme in which dysgerminoma represents the stage of earliest differentiation from which other non dysgerminomatous tumors may arise is presented. Although previously proposed for testicular germ cell neoplasia, this scheme has not yet been applied to their ovarian counterparts.

Adolescent↗