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Biomedical subjects

L G Koss

Publications and source records attributed to L G Koss.

At least 19 recordsLinked to original sources

Atypical endometrial hyperplasia shares genomic abnormalities with endometrioid carcinoma by comparative genomic hybridization.

Endometrial hyperplasia is a common disorder that is now observed with increasing frequency in women treated with hormonal replacement therapy or with tamoxifen. This study was undertaken to determine whether genomic features of various forms of endometrial hyperplasias would allow their classification as a benign, premalignant, or malignant abnormality. Comparative genomic hybridization (CGH) was performed on endometrial glands microdissected by laser capture microscope from 19 archival endometrial samples, comprising 5 normal endometria, 1 polyp, 2 simple hyperplasias, 5 hyperplasias with nuclear abnormalities (atypical hyperplasias), and 4 low-grade and 2 high-grade endometrioid carcinomas, 1 with squamous component (adenoacanthoma). Genomic DNA, extracted from the glands and the squamous component in 1 case, was amplified by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and compared with sex-matched DNA by CGH. No genomic imbalances were observed in the normal samples, the polyp, or the simple hyperplasias. However, in atypical hyperplasia, regardless of the level of cytologic atypia, genomic abnormalities were observed that also occurred in endometrioid carcinomas. Chromosomes 1, 8, and 10 were most often affected. The results are compared with molecular genetic abnormalities recently reported in these lesions. This study strongly suggests that atypical endometrial hyperplasias are closely related to endometrioid carcinoma and should be considered precancerous lesions, contrary to simple hyperplasia, which is a benign disorder. The squamous component of one of the high-grade carcinomas showed genetic abnormalities similar to those of endometrioid carcinoma and therefore does not represent squamous metaplasia but is an integral part of the malignant process.

Adult↗

Cytological recognition of invasive squamous cancer of the uterine cervix: comparison of conventional light-microscopical screening and neural network-based screening.

Cytologic recognition of invasive or microinvasive cancer of the uterine cervix may present substantial difficulties. In this study, we compared conventional light-microscopical screening of 109,104 cervical smears and neural network-based screening (NNS) of 245,527 smears, all obtained by the spatula-Cytobrush method. Two populations of Dutch women were included in the study: those receiving smears within the framework of the Dutch population screening program ("routine smears") and those receiving smears for other reasons, discussed in the text ("interval smears"). There were 71 smears, from an equal number of biopsy-confirmed invasive squamous carcinomas, 28 of which were microinvasive. The "interval smears" yielded a statistical valid higher prevalence of invasive cancer than "routine smears." Except for 5 smears that contained no evidence of abnormality ("sampling errors"), no false-negative errors occurred in the 52 NNS cases, whereas 4 such errors occurred in the 19 conventionally screened cases. By measuring the amount of cancerous material present in each smear (mapping), it could be documented that NNS was effective even in smears with a small number of cancer cells, whereas the 4 conventional false-negative screening errors occurred in smears of this type. The study showed that cells derived from invasive cancer of the cervix may have large bland nuclei that do not fit the images commonly associated with squamous cancer cells. Neural network-based screening of cervical smears was more effective than conventional screening in the diagnosis of invasive squamous cancer of the uterine cervix.

Carcinoma, Squamous Cell↗

Tenascin expression in intraepithelial neoplasia and invasive carcinoma of the uterine cervix.

OBJECTIVE: To determine whether the expression of the matrix protein tenascin (TN) is of diagnostic or prognostic value in cervical intraepithelial neoplasia (CIN). DESIGN: Tenascin expression was evaluated in 75 formalin-fixed, paraffin-embedded biopsy and surgical specimens of the uterine cervix. Specimens included 15 low-grade squamous neoplastic lesions (CIN I), 30 high-grade squamous neoplastic lesions (CIN II and CIN III), 5 microinvasive carcinomas, and 15 invasive squamous carcinomas. Five normal cervices and 5 examples of cervicitis were used as controls. Expression of TN was studied by immunohistochemistry with a monoclonal mouse anti-human tenascin antibody. Tenascin expression in the basement membrane and in the stroma was arbitrarily graded as normal or slightly, moderately, or markedly increased. RESULTS: In the normal cervix, TN formed a thin band along the basement membrane of the squamous epithelium, except for the transformation zone, where the bands splintered and delicate TN fibers were present in the adjacent stroma. In cervicitis, TN bands were splintered in the basement membrane and the protein was weakly expressed in the stroma infiltrated by inflammatory cells. In the 45 CIN lesions, regardless of grade, the TN bands in the basement membrane were slightly (25 cases) or moderately (20 cases) increased. In CIN lesions with chronic stromal inflammation, a slight increase in stromal staining was observed, similar to the findings in cervicitis. In microinvasive and frankly invasive squamous cell carcinomas, TN expression was markedly increased in the basement membrane and in the stroma surrounding the invasive nests of cancer cells. CONCLUSION: Tenascin expression may be of value in the assessment of early stromal invasion in cancer of the uterine cervix. Tenascin expression is of no value in distinguishing various grades of CIN and, therefore, is not a predictor of future behavior.

Carcinoma↗

Metastatic squamous-cell carcinoma in pericardial effusion: report of four cases, two with cardiac tamponade.

For reasons unknown, metastatic squamous-cell carcinoma is a rare cause of pleural effusions and is even less common in pericardial effusions. A review of all pericardial effusions examined in the Cytology Service at Montefiore Medical Center over a 15-year (1980-1994) period was undertaken (N = 251). Four cases with metastatic squamous-cell carcinoma were identified among 39 malignant effusions. Two patients with metastatic squamous-cell carcinoma presented with cardiac tamponade, and the other two cases had progressive cardiac failure. The diagnostic cells on cytology evaluation were scant in all four cases but exhibited classical features of metastatic squamous carcinoma, such as cytoplasmic keratinization, intercellular bridges, and occasional "pearl" formation. Pericardial biopsies available in three patients, two with cardiac failure and one with cardiac tamponade, were negative. In all four cases the primary tumor was a bronchogenic carcinoma. Metastatic squamous-cell carcinoma is an uncommon cause of pericardial effusion and usually indicates the presence of a bronchogenic carcinoma with a rapidly fatal outcome. Cytologic examination of pericardial fluid is essential in the evaluation of such patients.

Adult↗

Evaluation of esophageal cytology using a neural net-based interactive scanning system (the PAPNET system): its possible role in screening for esophageal and gastric carcinoma.

A neural net-based, semiautomated, interactive computerized cell analysis system (The PAPNET system, Neuromedical Systems, Suffern, NY) was used to examine cells from 138 esophageal smears obtained by lavage, brushings, or balloon from as many patients. From each smear, trained human observers examined 128 cell images selected by the machine. Abnormal cells were identified in all 35 patients with cancer, whether esophageal, gastric, oral, or metastatic. Further, in 11 smears, the displayed images allowed the recognition of effects of radiotherapy and, in 14 smears, the diagnosis of a specific tumor type, such as squamous cell carcinoma (8 patients) or adenocarcinoma (6 patients). In 3 additional cases, the diagnosis of "carcinoma, not further specified," was established. One case of esophageal carcinoma in situ, not previously recognized on a smear or in the biopsy specimen, and one case of gastric adenocarcinoma, not recognized in the smear, were identified in PAPNET-generated images. The possible application of the apparatus to the triage of smears and population screening for esophageal and gastric carcinoma precursors is discussed.

Adenocarcinoma↗

Characteristics of chromosomes in polarized normal human bronchial cells provide a blueprint for nuclear organization.

In normal human terminally differentiated and polarized bronchial cells, the fluorescent "painting" technique (FISH) for all chromosomes (except Y) documented that each homologue of each chromosome occupies a distinct, separate domain within the nucleus. The homologues are distributed along the nuclear membrane. In most cells and chromosomes studied, the two homologues were not identical: one was usually more "compact" than the other which was more "open," displaying fiber-shaped extensions. The differences between the territories of homologues 1 and 7 were shown to be statistically valid (P < 0.0001 by Wilcoxon sign rank test), as has been previously documented for the two X chromosomes (Eils et al., 1996). In some parallel arrays of bronchial cells, the position of the chromosomes in the nuclei was either identical or formed a mirror image, suggesting that the position of the chromosomes in polarized nuclei may be constant. To confirm this observation, the angles formed by the two homologues in the polarized oval nuclei were measured for chromosomes 1, X, and 7. The measurements disclosed that, in about two-thirds of the nuclei, the two homologues formed angles of 150 degrees, 157 degrees and 148 degrees, nearly identical to those formed by the same three chromosomes in prometaphase rosettes of cultured diploid human fibroblasts (Nagele et al., 1995). In about one third of the nuclei, the same homologues formed angles of 89 degrees, 72 degrees, and 94 degrees, and occasionally an angle of 180 degrees. A three-dimensional computer reconstruction of the nuclei was performed using the data for the X chromosomes. By cinematographic technique, it could be documented that the angles separating the two homologues depended on the rotation of the nucleus along the axes X, Y, and Z. The cause of the rotation is speculative at this time. Because of the concordance of these data in terminally differentiated epithelial cells with prior observations on prometaphases of human diploid fibroblasts, it is suggested that the position of chromosomes in all human cells is constant throughout the cell cycle. The possible significance of these observations is discussed.

Bronchoalveolar Lavage Fluid↗