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1.
Jpn J Clin Oncol ; 54(1): 31-37, 2024 Jan 07.
Article in English | MEDLINE | ID: mdl-37721176

ABSTRACT

OBJECTIVE: To investigate whether maintenance treatment could be safely and effectively performed with olaparib, olaparib plus bevacizumab and niraparib in platinum-sensitive advanced ovarian cancer at multiple institutions in Japan. METHODS: We investigated progression-free survival and adverse events in 117 patients with platinum-sensitive advanced ovarian cancer treated with maintenance therapy. RESULTS: The median progression-free survival of 117 patients was 20.1 months. Patients with germline BRCA pathogenic variants had a significantly better prognosis than the other groups (P < 0.001). Furthermore, in the multivariate analysis, stage IV (P = 0.016) and germline BRCA wild-type (P ≤ 0.001) were significantly associated with worse progression-free survival in patients with advanced ovarian cancer. Regarding adverse events, all three types of maintenance treatment were significantly worse than chemotherapy given before maintenance treatment with respect to renal function (olaparib, P = 0.037; olaparib plus bevacizumab, P < 0.001; and niraparib, P = 0.016). CONCLUSION: Maintenance treatment was performed effectively and safely. Renal function deterioration is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer.


Subject(s)
Ovarian Neoplasms , Humans , Female , Bevacizumab/adverse effects , Ovarian Neoplasms/pathology , Japan , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Phthalazines/adverse effects , Carcinoma, Ovarian Epithelial/drug therapy , Neoplasm Recurrence, Local/drug therapy , Maintenance Chemotherapy
2.
Gynecol Minim Invasive Ther ; 12(3): 148-152, 2023.
Article in English | MEDLINE | ID: mdl-37807995

ABSTRACT

Objectives: The objective was to investigate the microscopic artifacts made in the uterus of cervical high-grade squamous intraepithelial lesion (HSIL) resected by hysterectomy through minimally invasive (H-MI) procedures and to verify whether these specimens are suitable for histopathological assessment. Materials and Methods: This single-center retrospective study analyzed 28 patients with cervical HSIL, consisting of 21 premenopausal and seven postmenopausal women, who underwent H-MI. The proportion of the cervical mucosa covered by intact surface epithelium (residual ratio [RR]) was measured on microscopically. Surgical margin's status was also verified. Results: All cases developed detachment of the cervical surface epithelium to a varying extent. The RR was significantly higher in the premenopausal patients (median: 75.5%) than in the postmenopausal patients (median: 37.6%). Among the premenopausal patients, the RR was lower in the cases on whom uterine manipulator (UM) was used (median: 70.5%) than in the cases without UM use (median 92.7%). Among the 21 cases whose resected uterus contained HSIL, the vaginal resection margin was not assessable in three (14.2%) of the seven postmenopausal cases due to the artifact. Conclusion: Although transvaginal manipulation of the uterus causes detachment of the cervical surface epithelium, H-MI for cervical HSIL provides an acceptable specimen for histological assessment in premenopausal patients, even if UM is used. In postmenopausal women, H-MI easily develops artifactual loss of cervical surface epithelium, sometimes providing an unfavorable specimen for microscopic assessment.

3.
Anticancer Res ; 43(8): 3653-3658, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37500145

ABSTRACT

BACKGROUND/AIM: To determine if maintenance treatment can be performed effectively and safely in patients with platinum-sensitive relapsed ovarian cancer. PATIENTS AND METHODS: We carried out a multi-center study to investigate progression-free survival (PFS) and adverse events (AEs) in 229 patients receiving maintenance treatment for platinum-sensitive relapsed ovarian cancer. RESULTS: The median PFS in the 229 patients with maintenance treatment was 14.0 months (95% confidence interval=10.3-17.6 months). The hematological toxicities included ≥grade 3 anemia in 33.2% of cases. Anemia during maintenance treatment was significantly more common than anemia during chemotherapy given before maintenance treatment (p<0.001). Anemia during chemotherapy prior to maintenance treatment significantly increased the risk of anemia during maintenance treatment, compared with other clinical features (p<0.001). CONCLUSION: Maintenance treatment can be performed safely and effectively in patients with platinum-sensitive relapsed ovarian cancer. Anemia during chemotherapy given before maintenance treatment significantly increased the risk of developing anemia during maintenance treatment in patients with platinum-sensitive relapsed ovarian cancer.


Subject(s)
Anemia , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/drug therapy , Carcinoma, Ovarian Epithelial/drug therapy , Progression-Free Survival , Anemia/chemically induced , Neoplasm Recurrence, Local , Maintenance Chemotherapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects
4.
Gynecol Oncol Rep ; 34: 100676, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33304978

ABSTRACT

Post-transplant lymphoproliferative disorder (PTLD) refers to a group of diseases, characterized by abnormal proliferation of lymphocytes, that develop after organ transplantation. PTLD is associated with poor prognosis, and has become a major problem for transplant patients. In this report, we described a case of malignant lymphoma of the cervix in a bicollis uterus considered to be a PTLD in a patient after renal transplantation. The incidence of this disease is expected to increase as the survival rate of transplant patients improves. Hence, it is very important for gynecological oncologists to consider the presence of PTLD when examining such patients.

5.
Diagn Cytopathol ; 44(11): 912-916, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27381491

ABSTRACT

Seromucinous borderline tumors are typically confined to the ovaries and rarely relapse after surgery. We report the case of a woman with a seromucinous borderline tumor with peritoneal implant at the Douglas pouch, who was affected by a recurrent tumor at the vaginal stump 2 years and 6 months after the primary surgery. The recurrent lesion was detected by vaginal cytology. Histology of the recurrent lesion showed perineural infiltration, and progression to low-grade adenocarcinoma was suggested. After the second surgery, vaginal cytology showed that the tumor cells remained positive. At postoperative follow-ups of ovarian borderline tumors, an examination of the specific region where recurrence is likely to occur can contribute to the early detection of tumor relapse. Diagn. Cytopathol. 2016;44:912-916. © 2016 Wiley Periodicals, Inc.


Subject(s)
Adenocarcinoma/pathology , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/pathology , Vaginal Smears , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/surgery
6.
Hum Pathol ; 43(10): 1618-26, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22436624

ABSTRACT

The nature of "piling up" proliferation of clear cells in müllerian mucinous/mixed borderline tumor has not been well characterized. The purpose of this study was to clarify whether or not such clear cells represent concomitant clear cell neoplasms. First, we carefully reviewed hematoxylin and eosin slides taken from 139 ovarian tumors diagnosed as clear cell carcinoma (112 cases) and müllerian mucinous/mixed borderline tumor (27 cases) to clarify (1) the frequency of piling-up clear cells in müllerian mucinous/mixed borderline tumor and (2) the frequency of the coexistence of typical clear cell carcinoma and müllerian mucinous/mixed borderline tumor. Second, we investigated the immunohistochemical expression of estrogen receptor, hepatocyte nuclear factor-1ß, and glypican-3 in proliferating clear cells in both tumors. We identified piling-up clear cells in 56% of müllerian mucinous/mixed borderline tumors. Such clear cells lacked the severe nuclear atypia, complex branching, and dense hyalinized cores of typical clear cell carcinoma. We did not find coexistence of typical clear cell carcinoma and müllerian mucinous/mixed borderline tumor in any tumors. Piling-up clear cells and endocervical-like mucinous cells were positive for estrogen receptor but negative for hepatocyte nuclear factor-1ß and glypican-3. Most clear cell carcinomas showed a hepatocyte nuclear factor-1ß-positive/estrogen receptor-negative immunophenotype, and about half of them were glypican-3 positive. In conclusion, piling-up clear cells in müllerian mucinous/mixed borderline tumor do not represent concomitant clear cell neoplasms because clear cell carcinoma and müllerian mucinous/mixed borderline tumor hardly ever coexist and because such clear cells in both tumors are immunophenotypically distinct.


Subject(s)
Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Mucinous/pathology , Ovarian Neoplasms/pathology , Adenocarcinoma, Clear Cell/metabolism , Adenocarcinoma, Mucinous/metabolism , Female , Glypicans/biosynthesis , Hepatocyte Nuclear Factor 1-beta/biosynthesis , Humans , Immunohistochemistry , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/metabolism , Ovarian Neoplasms/metabolism , Receptors, Estrogen/biosynthesis
7.
Hum Pathol ; 43(6): 808-17, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22079356

ABSTRACT

We recently have demonstrated nuclear localization of E-cadherin in ovarian adult granulosa cell tumors (Histopathology 2011;58:423). The purpose of the present study is to investigate the diagnostic utility of E-cadherin nuclear staining for the differential diagnosis between ovarian adult granulosa cell tumor and its morphological mimics. Tissue samples taken from 81 ovarian tumors and 20 extraovarian tumors were immunohistochemically stained using monoclonal anti-E-cadherin antibody recognizing cytoplasmic domain (clone 36 supplied by BD Biosciences, San Jose, CA). The ovarian tumors consisted of 30 adult granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 5 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 18 endometrioid adenocarcinomas, and 10 poorly differentiated serous adenocarcinomas. Extraovarian tumors consisted of 16 uterine endometrial stromal neoplasms and 4 pulmonary small cell carcinomas. Only tumor cells with nuclear staining were considered positive in this study. Ninety percent of adult granulosa cell tumors, 67% of Sertoli-stromal cell tumors, 64% of fibrothecomas, 75% of endometrial stromal neoplasms, 75% of small cell carcinomas, and the one large cell neuroendocrine carcinoma showed E-cadherin nuclear expression, whereas all the ovarian carcinoid tumors, endometrioid adenocarcinomas, and poorly differentiated serous adenocarcinomas were negative. E-cadherin nuclear staining is useful in distinguishing between adult granulosa cell tumors and ovarian adenocarcinomas or carcinoid tumors. However, it is of limited use for distinguishing between adult granulosa cell tumors and endometrial stromal neoplasms or small cell carcinomas. E-cadherin should be included in the immunohistochemical panel for an accurate diagnosis of ovarian adult granulosa cell tumors.


Subject(s)
Cadherins/genetics , Granulosa Cell Tumor/diagnosis , Granulosa Cell Tumor/genetics , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Base Sequence , Cadherins/biosynthesis , Cell Nucleus/metabolism , DNA Mutational Analysis , Diagnosis, Differential , Female , Granulosa Cell Tumor/metabolism , Humans , Immunohistochemistry , Ovarian Neoplasms/metabolism
8.
Surg Today ; 41(4): 542-5, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21431489

ABSTRACT

A 48-year-old woman developed a mobile abdominal mass in the course of treatment for recurrent breast cancer. Imaging studies indicated linitis plastica of the colon. She underwent surgery because of the stenosis of the transverse colon. An examination of the resected specimen revealed a segmental stricture, thickening of the entire wall, and a granular mucosa resembling cobblestones. Microscopic findings of the colon lesion were very similar to those of her primary, invasive lobular carcinoma of the breast. Atypical cells showed immunoreactivity for cytokeratin-7, but not for cytokeratin-20. These findings suggested that the lesion of the colon was a colonic metastasis of breast cancer. Metastatic gastrointestinal diseases originating from breast carcinoma are unusual, and colonic metastases are especially rare. Although colon cancer may occur in patients with a history of breast cancer, metastatic colon cancer should be suspected if linitis plastica is detected.


Subject(s)
Breast Neoplasms/pathology , Colonic Neoplasms/secondary , Biomarkers, Tumor/analysis , Breast Neoplasms/surgery , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/surgery , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Linitis Plastica/diagnosis , Lymph Node Excision , Mastectomy , Middle Aged , Neoplasm Invasiveness , Radiography
9.
Histopathology ; 58(3): 423-32, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21299609

ABSTRACT

AIMS: The role of misregulated Wnt/beta-catenin signalling in human ovarian granulosa cell tumour (GCT) has not been well characterized. The aim of this study was to confirm subcellular localization of key molecules of Wnt signalling (beta-catenin and E-cadherin) in human ovarian GCTs. METHODS AND RESULTS: Tissue samples taken from 32 human ovarian GCTs and 19 human normal ovaries containing 68 follicles were stained immunohistochemically using monoclonal anti-beta-catenin and anti-E-cadherin antibodies. None of the 32 GCTs and none of the 68 ovarian follicles showed beta-catenin nuclear expression (0%). On the other hand, 28 of 32 GCTs (88%) and 53 of 68 normal ovarian follicles (78%) showed nuclear expression of E-cadherin in granulosa cells. The ovarian stroma in all 19 normal ovaries showed nuclear expression of E-cadherin but not beta-catenin. Membranous and cytoplasmic expression was observed variously in ovarian GCT, follicles and stroma. CONCLUSIONS: We have confirmed frequent nuclear localization of E-cadherin but not beta-catenin in human ovarian GCT, ovarian follicles and stroma. There is no evidence of misregulated Wnt/beta-catenin signalling (represented by nuclear expression of beta-catenin) in human ovarian GCT. Nuclear translocation of E-cadherin might contribute to ovarian folliculogenesis or granulosa/stromal cell differentiation.


Subject(s)
Cadherins/analysis , Cell Nucleus/metabolism , Granulosa Cells/metabolism , Ovarian Follicle/metabolism , Ovarian Neoplasms/metabolism , beta Catenin/metabolism , Cadherins/metabolism , Female , Granulosa Cell Tumor/metabolism , Granulosa Cell Tumor/pathology , Granulosa Cells/pathology , Humans , Ovarian Follicle/pathology , Ovarian Neoplasms/pathology , Ovary/metabolism , Ovary/pathology , Signal Transduction
10.
Oncol Rep ; 24(6): 1569-76, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21042753

ABSTRACT

Ovarian mucinous neoplasms of gastro-intestinal type (GI-type) are known to be a heterogeneous tumor composed of benign, borderline and non-invasive and invasive malignant lesions. The presence of infiltrative invasion is also known to be an important prognostic factor of this neoplasm. Laminin γ 2 chain, known to stimulate tumor cell invasion and migration, has not been sufficiently investigated in ovarian mucinous neoplasms. The purpose of this study was thus to clarify the role of laminin γ 2 in ovarian mucinous neoplasms of GI-type. We selected each morphological phase of tumor development from 61 cases of mucinous neoplasms of the GI-type: 55 adenoma lesions, 60 borderline lesions, 20 microinvasive lesions, 17 intraepithelial carcinoma lesions, 38 expansile invasive carcinoma lesions, 19 infiltrative invasive carcinoma lesions and 5 mural nodules lesions; and evaluated the localization of laminin γ 2 in the lesions using immunohistochemical method. The staining pattern was classified into i) basement membranous (BM), ii) cytoplasmic (CYT) and iii) stromal (S) pattern. The BM pattern was characteristic in adenoma, borderline, and interaepithelial and expansile invasive carcinoma lesions. The CYT and S patterns were characteristic in infiltrative invasive lesions. The staining pattern of mural nodules was similar to that of infiltrative invasion. The infiltrative invasion of GI-type ovarian mucinous neoplasms may be promoted by cytoplasmic and/or stromal expression of laminin γ 2 chain.


Subject(s)
Adenocarcinoma, Mucinous/pathology , Gastrointestinal Neoplasms/pathology , Laminin/metabolism , Neoplasm Staging/methods , Ovarian Neoplasms/secondary , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/metabolism , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Cohort Studies , Cytoplasm/metabolism , Disease Progression , Female , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/metabolism , Humans , Models, Biological , Neoplasm Invasiveness , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Prognosis , Stromal Cells/metabolism , Stromal Cells/pathology
12.
Mod Pathol ; 23(2): 225-34, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19898427

ABSTRACT

Aberrant activation of the Wnt signaling pathway has been implicated in tumorigenesis of a wide range of tumors, including colorectal cancer. Regarding endometrial stromal tumors and related high-grade sarcomas, there have been some reports regarding nuclear accumulation of beta-catenin. To clarify the function of the aberrant Wnt signaling pathway in these tumors, we searched for mutations of the CTNNB1 (beta-catenin) gene and APC gene by PCR direct sequencing and analyzed the methylation status of SFRP genes. We also examined overexpression of cyclin D1 and MMP-7, which are direct target genes of beta-catenin. Eight endometrial stromal nodules, 16 low-grade endometrial stromal sarcomas, and 13 undifferentiated endometrial sarcomas were examined. PCR and direct sequencing revealed no mutation of the beta-catenin gene or the APC gene. Concerning the promoter methylation status of SFRP genes, methylation-specific PCR revealed no significant difference between the group with nuclear beta-catenin expression and that without nuclear beta-catenin expression. Immunohistochemistry revealed overexpression of cyclin D1 in 2 out of 8 endometrial stromal nodules, 1 out of 17 low-grade endometrial stromal sarcomas, and 6 out of 13 undifferentiated endometrial sarcomas, and these 6 undifferentiated endometrial sarcomas simultaneously expressed nuclear beta-catenin. Interestingly, all six undifferentiated endometrial sarcoma cases with cyclin D1 overexpression histologically featured rather uniform nuclei. In contrast, the six cases of undifferentiated endometrial sarcoma with highly pleomorphic nuclei were all negative for cyclin D1. In conclusion, among endometrial stromal tumors and related sarcomas, undifferentiated endometrial sarcomas featuring uniform nuclei were characterized by frequent coincident expression of beta-catenin and cyclin D1. This finding raises the possibility that cyclin D1 is upregulated by beta-catenin in these high-grade sarcomas previously called high-grade endometrial stromal sarcoma.


Subject(s)
Cyclin D1/biosynthesis , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Sarcoma, Endometrial Stromal/metabolism , Sarcoma, Endometrial Stromal/pathology , beta Catenin/biosynthesis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Cell Nucleus/pathology , Co-Repressor Proteins , Cyclin D1/genetics , DNA Methylation , DNA Mutational Analysis , DNA-Binding Proteins , Endometrial Neoplasms/genetics , Female , Genes, APC , Glycoproteins/biosynthesis , Glycoproteins/genetics , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins , Matrix Metalloproteinase 7/biosynthesis , Matrix Metalloproteinase 7/genetics , Middle Aged , Mutation , Neoplasm Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sarcoma, Endometrial Stromal/genetics , Signal Transduction/physiology , Transcription Factors/genetics , Young Adult , beta Catenin/genetics
14.
Hum Pathol ; 40(8): 1168-75, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19368953

ABSTRACT

Hobnail-like cells, which suggest a diagnosis of clear cell carcinoma, are also focally observed in serous borderline tumor of the ovary, causing diagnostic confusion. However, the precise nature of hobnail-like cells in serous borderline tumor has not been well characterized. The purpose of this study was to clarify whether or not hobnail-like cells in serous borderline tumor represent concomitant incipient clear cell neoplasms. First, we carefully reviewed hematoxylin and eosin slides taken from 115 ovarian tumors diagnosed as clear cell carcinoma (73 cases), mixed adenocarcinoma containing clear cell carcinoma (5 cases), and serous borderline tumor (37 cases) to clarify the frequency of coexistence of typical clear cell carcinoma and serous borderline tumor. Through the hematoxylin and eosin review, we paid special attention to the cytologic features of hobnail-like cells in serous borderline tumor and serous borderline tumor-like papillary areas in clear cell carcinoma. Second, we selected 19 serous borderline tumors and 16 clear cell carcinomas, in which hobnail-like cells were easily recognizable, and investigated the immunohistochemical expression of estrogen receptor and Wilms tumor gene protein. No coexistence of clear cell carcinoma and serous borderline tumor was evident in any of the above 115 ovarian tumors. Hobnail-like cells were focally positive for estrogen receptor and Wilms tumor gene protein in nearly all serous borderline tumors. Hobnail-like cells in all clear cell carcinomas were completely negative for estrogen receptor and Wilms tumor gene protein, although estrogen receptor expression was very focally observed (less than 5% area) in non-hobnail cells of only one clear cell carcinoma. In conclusion, hobnail-like cells in serous borderline tumor do not represent concomitant incipient clear cell neoplasms because (1) clear cell carcinoma and serous borderline tumor do not coexist and (2) hobnail-like cells in clear cell carcinoma and serous borderline tumor are immunophenotypically distinct. Recognition of our conclusion may protect a patient with "conspicuous hobnail-like cells in serous borderline tumor" from an erroneous overdiagnosis of "concomitant clear cell carcinoma admixed with serous borderline tumor."


Subject(s)
Adenocarcinoma, Clear Cell/diagnosis , Cystadenocarcinoma, Serous/diagnosis , Ovarian Neoplasms/diagnosis , Precancerous Conditions/diagnosis , Adenocarcinoma, Clear Cell/metabolism , Biomarkers, Tumor/metabolism , Cell Cycle Proteins , Cystadenocarcinoma, Serous/metabolism , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Middle Aged , Nuclear Proteins/metabolism , Ovarian Neoplasms/metabolism , Precancerous Conditions/metabolism , RNA Splicing Factors , Receptors, Estrogen/metabolism
15.
Hum Pathol ; 40(7): 965-74, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19269675

ABSTRACT

Mullerian mucinous borderline tumor and gastrointestinal mucinous borderline tumor are considered mucinous tumor subtypes. However, it has been reported that mullerian mucinous borderline tumor shares many clinicopathologic features with serous borderline tumor. Furthermore, some investigators have explained the histogenesis of mullerian mucinous borderline tumor by metaplastic and hyperplastic transformation of endometriosis (Fukunaga M, Ushigome S. Epithelial metaplastic changes in ovarian endometriosis. Mod Pathol. 1998;11:784-788). The purpose of this study is to substantiate the concept that mullerian mucinous borderline tumor is histogenetically closer to serous borderline tumor or low-grade endometrioid tumor than to gastrointestinal mucinous borderline tumor by directly comparing their immunophenotype. A total of 80 cases of low-grade ovarian tumors composed of 20 mullerian mucinous borderline tumors, 20 gastrointestinal mucinous borderline tumors, 20 serous borderline tumors, and 20 low-grade endometrioid tumors were immunohistochemically evaluated for the expression of estrogen receptor, progesterone receptor, vimentin, WT-1, beta-catenin, and PTEN. Almost all cases of mullerian mucinous borderline tumor, serous borderline tumor, and low-grade endometrioid tumor showed diffuse and strong nuclear expression of estrogen receptor and progesterone receptor. In addition, about half of the mullerian mucinous borderline tumor, serous borderline tumor, and low-grade endometrioid tumor cases showed focal but strong vimentin cytoplasmic expression. In contrast, gastrointestinal mucinous borderline tumor showed no expression of estrogen receptor, progesterone receptor, or vimentin, except for 1 case in which estrogen receptor expression was very focally and weakly observed. WT-1 nuclear expression was observed in most serous borderline tumors and only 15% of low-grade endometrioid tumor, but mullerian and gastrointestinal mucinous borderline tumor cases were completely negative. beta-Catenin nuclear expression was significantly more frequent in low-grade endometrioid tumor than in mullerian mucinous borderline tumor, gastrointestinal mucinous borderline tumor, or serous borderline tumor. PTEN expression was significantly lower in low-grade endometrioid tumor than in mullerian mucinous borderline tumor, gastrointestinal mucinous borderline tumor, and serous borderline tumor. Multiple comparisons of quantitative immunoreactivities of estrogen receptor, progesterone receptor, and vimentin revealed that the gastrointestinal mucinous borderline tumor expression profiles were significantly different from those of mullerian mucinous borderline tumors, serous borderline tumors, and low-grade endometrioid tumors. The immunohistochemical expression profiles of estrogen receptor, progesterone receptor, and vimentin substantiate the concept that the histogenesis of mullerian mucinous borderline tumor is closer to those of serous borderline tumor and low-grade endometrioid tumor than to that of gastrointestinal mucinous borderline tumor. However, aberrant beta-catenin and PTEN protein expression, both of which are known to contribute to the tumorigenesis of low-grade endometrioid tumor, appeared to be less important for the tumorigenesis of mullerian mucinous borderline tumor.


Subject(s)
Adenocarcinoma, Mucinous/pathology , Carcinoma, Endometrioid/pathology , Genital Neoplasms, Female/pathology , Ovarian Neoplasms/pathology , Adenocarcinoma, Mucinous/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/metabolism , Female , Genital Neoplasms, Female/metabolism , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/metabolism , PTEN Phosphohydrolase/analysis , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Vimentin/analysis , WT1 Proteins/analysis , beta Catenin/analysis
17.
Pathol Int ; 58(12): 757-64, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19067849

ABSTRACT

Ovarian mature cystic teratomas (MCT) uncommonly undergo malignant transformation to squamous cell carcinoma (SCC). While alterations in the p53 tumor suppressor gene and protein have been shown, few studies have analyzed other molecular changes leading to this malignant conversion. The purpose of the present study was to investigate 21 samples of SCC arising in MCT for altered expression in known p53- and p16/Rb-dependent cell cycle regulatory proteins, and the association between their expression and cellular proliferation and histological features. Overexpression of the p53 protein was observed in 14 SCC (67%), while four (19%) had point mutations in the p53 gene. Reduced expression of the p16 protein was observed in 18 SCC (86%), while p16 gene alterations (hypermethylation (29%) and point mutation (33%)) were found in 11 (52%). Furthermore, a statistically significant correlation was observed between p53 and Rb overexpression (P=0.0010), and the overexpression of both p53 and Rb was respectively significantly correlated with increased cellular proliferation. The results indicate that alterations in both the p53 and p16-Rb pathways are associated with SCC arising in MCT.


Subject(s)
Carcinoma, Squamous Cell/genetics , Cell Transformation, Neoplastic/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Gene Expression Regulation, Neoplastic , Ovarian Neoplasms/genetics , Teratoma/genetics , Tumor Suppressor Protein p53/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p16/metabolism , DNA Methylation , DNA Mutational Analysis , Female , Gene Silencing , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Point Mutation , Teratoma/metabolism , Teratoma/pathology , Tumor Suppressor Protein p53/metabolism
18.
Am J Surg Pathol ; 32(8): 1228-38, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18580489

ABSTRACT

Classification and terminology of non-low-grade endometrial sarcomas, which show significant nuclear atypia, have been controversial. Currently, these tumors seem to be classified all together into "undifferentiated endometrial sarcoma (UES)." However, it remains unclear whether these non-low-grade sarcomas are universally "undifferentiated." We divided these sarcomas morphologically into undifferentiated endometrial sarcoma with nuclear uniformity (UES-U) and undifferentiated endometrial sarcoma with nuclear pleomorphism (UES-P), and compared their molecular genetic and immunohistochemical profiles. Eighteen low-grade endometrial stromal sarcomas (ESS-LG), 7 UES-U, and 6 UES-P were examined. All the patients with ESS-LG were still alive, either with or without disease, whereas 4 of the 5 patients with advanced stage UES-U and all 3 of the patients with advanced stage UES-P had died of the disease. JAZF1-JJAZ1 fusion transcript was detected in 6 (50%) out of 12 ESS-LG and in 1 (33%) of 3 UES-U, whereas it was not detected in any of the cases of UES-P. ESS-LG and UES-U frequently showed positive immunoreaction for estrogen receptor (ESS-LG: 94%, UES-U: 57%) and progesterone receptor (ESS-LG: 94%, UES-U: 57%), whereas all the UES-P were negative for these receptors. Nuclear beta-catenin expression was more frequently recognized in ESS-LG (47%) and UES-U (85%), compared with UES-P (33%). Moreover, nuclear accumulation of p53 and TP53 gene missense mutations were limited to 3 UES-P cases. Our data suggest that UES-U shares some molecular genetic and immunohistochemical characteristics with ESS-LG, but UES-P considerably differs from ESS-LG.


Subject(s)
Biomarkers, Tumor , Cell Nucleus/chemistry , DNA Mutational Analysis , Endometrial Neoplasms , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Reverse Transcriptase Polymerase Chain Reaction , Sarcoma, Endometrial Stromal , Adult , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Cell Differentiation , Cell Nucleus/pathology , Co-Repressor Proteins , DNA-Binding Proteins , Endometrial Neoplasms/chemistry , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/therapy , Female , Humans , Middle Aged , Neoplasm Proteins/genetics , Neoplasm Staging , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Sarcoma, Endometrial Stromal/chemistry , Sarcoma, Endometrial Stromal/genetics , Sarcoma, Endometrial Stromal/pathology , Sarcoma, Endometrial Stromal/therapy , Transcription Factors/genetics , Treatment Outcome , Tumor Suppressor Protein p53/analysis , Tumor Suppressor Protein p53/genetics , beta Catenin/analysis
19.
Mol Med Rep ; 1(6): 797-803, 2008.
Article in English | MEDLINE | ID: mdl-21479488

ABSTRACT

Solitary fibrous tumors (SFTs) are rare spindle cell tumors that usually arise in the pleura, although they also occur in extrapleural sites. SFTs usually have a favorable clinical course; however, a small number of metastasizing cases have been reported. We evaluated the detailed clinicopathological findings of 20 extrapleural and 16 pleural SFTs. Among them, 6 cases of the histologically malignant variant (4 extrapleural and 2 pleural tumors) were identified. According to the follow-up data, none of the cases, including the 6 malignant tumors, developed metastases in this series. There were no significant differences in the histologic findings between the extrapleural and pleural SFTs. Tumor necrosis was frequently associated with the malignant variant. Immunohistochemically, malignant SFTs revealed more frequent p53 expression (4/6) compared with ordinary SFTs (2/30) (P=0.0027). The MIB-1 labeling index (LI) was significantly higher in malignant SFTs (mean 13.48) than in ordinary SFTs (mean 7.27) (P=0.0023). Our results indicate that tumor necrosis, p53 expression and a high MIB-1 LI are additional parameters of the malignant variant of SFTs, although they do not necessarily have predictive value for biological behavior. Further studies are required to find reliable molecular biomarkers for predicting the clinical outcome of patients with this unique tumor.

20.
Nihon Shokakibyo Gakkai Zasshi ; 104(9): 1383-6, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17827911

ABSTRACT

A 85-year-old Japanese woman was urgently admitted to our hospital complaining of vomiting 20 months after the initial diagnosis of Merkel cell carcinoma on the right eyelid. The patient died of a huge intra-abdominal mass with complete obstruction of the distal duodenum two months later. On autopsy, the mass measuring 18 x 12 x 5 cm in size was histologically diagnosed as metastatic Merkel cell carcinoma and directly invaded the stomach, pancreas, and distal duodenum.


Subject(s)
Abdominal Neoplasms/secondary , Carcinoma, Merkel Cell/secondary , Duodenal Obstruction/etiology , Lymph Nodes/pathology , Skin Neoplasms/pathology , Aged, 80 and over , Duodenal Neoplasms/secondary , Female , Humans , Lymphatic Metastasis , Pancreatic Neoplasms/secondary , Stomach Neoplasms/secondary
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