High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability.

The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors.

Morphologic characteristics of p16INK4a-positive cells in cervical cytology samples.

Objective: Overexpression of p16INK4a has been proposed as a biomarker helpful for the identification of dysplastic cervical epithelial cells on histologic slides as well as in cervical smears. Since a few nontransformed cells in the genital tract in some instances may also express p16INK4a, we evaluated whether applying established morphologic criteria for cervical dysplasia allows a distinction of dysplastic from nondysplastic p16INK4a-stained cells in cytologic samples.

Study Design: Liquid-based cytology samples were obtained from a screening population (n=50), and from patients attending a dysplasia clinic (n=40).

Traditional and new molecular methods for early detection of cervical cancer.

Disadvantages of the traditional Papanicolaou-method for the cytological detection of cervical carcinomas and their precursors can be overcome by the use of specific molecular markers for nuclear attypicality. High grade HR-HPV induced cervical dysplasia is initiated by deregulated expression of viral oncogenes in replicating epithelial stem cells. Here, the E6-E7 gene products gain control of cell cycle and mitotic activity first and induce multistep mutagenesis with severe genomic instability in successin.

Molecular analysis of endometrial hyperplasia in HNPCC-suspicious patients may predict progression to endometrial carcinoma.

Women predisposed to hereditary nonpolyposis colorectal cancer are at high risk of developing endometrial carcinoma at a young age. Hereditary nonpolyposis colorectal cancer-associated endometrial carcinomas are of the endometrioid type, usually arise from complex atypical hyperplasia, and often show microsatellite instability. To identify occult hereditary nonpolyposis colorectal cancer individuals among endometrial carcinoma patients, we examined complex atypical hyperplasias and endometrial carcinomas of 60 women < or =50 years of age (mean age: 35.

Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri.

Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false-positive and false-negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing.

The endometrium in breast cancer patients on tamoxifen.

We restudied histologically and immunohistochemically 17 endometrial carcinomas, 2 malignant mixed tumors and 180 endometria with benign changes during or after tamoxifen therapy. The carcinomas were subtyped according to the 1994 WHO-classification. Endometrial biopsies were taken only if the endometrial thickness was > 8 mm sonographically, when a polyp was seen, or for postmenopausal bleeding.

Histopathology of functional and neoplastic changes in cervix and endometrium.

Over 90% of all cervical carcinomas originate from hyperplastic reserve cells of the endocervix. When cell cycles of the pluripotent reserve cells are shortened or damaged by hormonal overstimulation or toxic chemicals, DNA repair after viral infection is no longer possible. The immortalized cells may then become malignant with precancerous and carcinomatous differentiation to squamous, adenosquamous or adenocarcinomas.

Changes in the endometrium caused by endogenous hormonal dysfunction.

The endometrium responds precisely and predictably to every hormonal dysfunction that may result from absent, deficient or excessive hormone production caused by an arrest of follicular maturation at different stages. Anovulatory failures may be due to arrest of follicular development and may cause endometrial atrophy or deficient proliferation. Arrest of follicular regression may result in irregular proliferation or various degrees of hyperplasia.

Lower frequency of allele loss on chromosome 18q in human breast cancer than in colorectal tumors.

Inactivation of tumor suppressor genes is thought to be a critical step in tumorigenesis. The DCC (deleted in colorectal carcinoma) gene, located on the long arm of chromosome 18, has been shown to be frequently deleted in colorectal tumors. To investigate the involvement of allelic deletions on chromosome 18q in breast cancer tumorigenesis we analyzed 28 primary breast tumors and 28 colorectal tumors (24 carcinomas, 4 adenomas) with four different polymorphic DNA markers detecting RFLPs on chromosome 18q.

[Morphologic endometrium changes with tamoxifen].

Women receiving tamoxifen as adjuvant therapy for breast cancer usually develop atrophy of the endometrium. Cystic polyps as well as endocervical and clear-cell metaplasias also frequently arise in the these atrophic endometria. The invasive endometrial carcinomas we have observed in these women have all been until now either mucinous, clear-cell or serous-papillary carcinomas, that is, different from the endometrioid type of adenocarcinomas that arise under estrogenic stimulation.

Mucinous and clear cell adenocarcinomas of the endometrium in patients receiving antiestrogens (tamoxifen) and gestagens.

In recent years, tamoxifen therapy for breast carcinoma has been associated with endometrial carcinoma with increasing frequency. We describe 10 cases of this association as well as 12 cases of endometrial carcinoma after therapy with synthetic gestagens. All but one of the 22 carcinomas we describe here were of the mucinous or clear cell type, and arose in atrophic endometria containing foci of mucinous (endocervical) and clear cell metaplasia.

[Receptivity of the endometrium: comparison of ultrasound and histologic findings after hormonal stimulation].

On the day of the scheduled embryo transfer, endometrial biopsies were taken from 53 patients of an IVF-programme. There was subsequent failure of fertilisation in all of these patients. The histologic pattern, compared with reflectivity and thickness of the endometrium was determined sonographically on the same day.

[Role of steroid hormones and related biological substances in the etiology of endometrial carcinomas].

Synthetical oestrogens, as well as gestagens may cause metaplastic changes of the endometrial epithelia. While squamous and tubal metaplasia are most often due to oestrogenic stimulation and develop in hyperplastic endometria, mucinous and clear cell metaplasia are stimulated by gestagens and tamoxifen. Tamoxifen seems to act gestagen-like on the endometrium.

[New cytogenetic classification of precancerous lesions and carcinomas of the endometrium: possibilities and limits of immunohistochemical differentiation].

Various grades of adenomatous hyperplasia represent precancerous states leading to the most common type of adenocarcinoma with endometrial differentiation. Grades 1 and 2 are characterized by architectural abnormalities only (complex hyperplasia). They rarely progress to carcinoma.

The value of immunohistochemistry in the differential diagnosis of endometrial carcinomas.

Endometrial carcinomas may originate from endometrial glandular epithelium and show endometrial differentiation, or from various types of metaplasias developing in the endometrium from pluripotent Müllerian epithelium. They then show endocervical or serous papillary differentiation. Because of their differences in spread, speed of growth and survival rates, it is important to subclassify these endometrial carcinomas.

Immunohistochemical studies on uterine tumors. I. Invasive squamous cell carcinomas of the cervix and their precursors.

40 invasive carcinomas and 80 preinvasive lesions of the uterine cervix were studied immunohistochemically; 40 benign lesions served as controls. On histological and immunohistochemical examination, invasive and preinvasive carcinomas were subdivided in the squamous (large cell, ectocervical) type and the reserve cell (small, large or clear cell, endocervical) type. Immunohistochemically, 100% of the invasive and preinvasive squamous cell carcinomas were positive with anticytokeratins 13, 14, 16 and negative with anticytokeratin 8 and anti-CEA.

The histogenetic origin of cervical mesonephric hyperplasia and mesonephric adenocarcinoma of the uterine cervix studied with immunohistochemical methods.

Forty-four cases of mesonephric hyperplasia (MH) and two adenocarcinomas arising from mesonephric remnants (MA) in the cervix were compared immunohistochemically with 10 embryonic and fetal mesonephric tissues. The mesonephric cells retained their pattern for intermediate filaments during ontogenesis, as well as in the mature, hyperplastic, and neoplastic states: they expressed cytokeratin 8, cytokeratin 13, and vimentin, the two latter in variable amounts. In embryonic mesonephric tissues, cytokeratin was absent, whereas the staining for vimentin was intense.