Kinetics of cell replication in the uterine cervix. VII. Loci of mitotic basal cells during cervical carcinogenesis

The frequency and the topographic occurrence (i.e., loci) of vincristine-arrested mitosis in the basal-cell layer was studied during the process of cervical carcinogenesis in C57B1 mice. The total frequency of mitosis decreased (by comparison to controls) not only in cervical intraepithelial neoplasias of grades I, II and III and in invasive carcinomas, but also in the normal epithelium of carcinogen-treated animals. This confirms earlier results and suggests that the pace of replication of cells in contact with the stroma is decreased during carcinogenesis. On the other hand, the proportion of the number of mitotic basal cells occurring singly or in groups of 2, 3 or greater than or equal to 4, as well as the proportion of loci with 1, 2, 3 or greater than or equal to 4 mitoses, were similar during cervical carcinogenesis (when compared to controls). It would thus appear that the proliferation of the cervical epithelium during carcinogenesis is regulated by two factors: one that seems to diminish the total number of mitotic basal cells during carcinogenesis, and another that seems to maintain as constant the proportion of mitotic loci, both under normal conditions and throughout the development of intraepithelial neoplasias, in the uterine cervix.     

DNA replication in synchronized cultured mammalian cells : VI. The temporal replication of ribosomal cistrons in synchronized cell lines

The time of synthesis of ribosomal genes was studied in a haploid (Rana pipiens), and a pseudodiploid (Chinese hamster) cell line. R. pipiens cells were synchronized by amethopterin block. Chinese hamster cells were synchronized by isoleucine starvation followed by hydroxyurea treatment. DNA replicated during three or four selected intervals of the S period was separated from the remainder of the DNA by bromodeoxyuridine density labeling. Purified bromodeoxyuridine substituted DNA was annealed with radioactive-labeled 28S ribosomal RNA (rRNA) to determine when, during different intervals of S, the nuclear DNA homologous to rRNA was replicated. In the R. pipiens and Chinese hamster cell lines, the percent of nuclear DNA homologous to 28S rRNA is highest in the DNA replicated during the first half of the S period.     

Human immunodeficiency virus infection of cells arrested in the cell cycle.

Cell proliferation is necessary for proviral integration and productive infection of most retroviruses. Nevertheless, the human immunodeficiency virus (HIV) can infect non-dividing macrophages. This ability to grow in non-dividing cells is not specific to macrophages because, as we show here, CD4+ HeLa cells arrested at stage G2 of the cell cycle can be infected by HIV-1. Proliferation is necessary for these same cells to be infected by a murine retrovirus, MuLV. HIV-1 integrates into the arrested cell DNA and produces viral RNA and protein in a pattern similar to that in normal cells. In addition, our data suggest that the ability to infect non-dividing cells is due to one of the HIV-1 core virion proteins. HIV infection of non-dividing cells distinguishes lentiviruses from other retroviruses and is likely to be important in the natural history of HIV infection.     

DNA-synthesizing T and non-T cells in chronic lymphocytic leukemia.

In 21 patients with chronic lymphocytic leukemia (CLL) and in 8 hematologically normal persons the number of DNA-synthesizing peripheral blood lymphocytes was investigated by autoradiographic techniques. The lymphocytes were differentiated by EN-rosette tests into T and non-T lymphoid cells. The results show a normal number of proliferating T lymphoid cells and an increased number of proliferating non-T lymphoid cells in clinical stages O-I. Stages III-IV demonstrate a significant increase of the proliferation rate of both T and non-T lymphoid cells. The possible pathogenetic factors and the prognostic value of these results are discussed.     

Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix.

Minichromosome maintenance proteins (Mcm) 2-7 play essential roles in eukaryotic DNA replication. Several reports have indicated the usefulness of Mcm proteins as markers of cancer cells in histopathological diagnosis. However, their mode of expression and pathophysiological significance in cancer cells remain to be clarified. We compared the level of expression of Mcm proteins among human HeLa uterine cervical carcinoma cells, SV40-transformed human fibroblast GM00637 cells and normal human fibroblast WI-38 cells. All the proteins examined were detected in HeLa and GM cells at 6-10 times the level found in WI-38 cells on average. This increase was observed both in total cellular proteins and in the chromatin-bound fraction. Consistently, Mcm2 mRNA was enriched in HeLa cells to approximately four times the level in WI-38 cells, and the synthesis of Mcm4, 6 and 7 proteins was accelerated in HeLa cells. Immunohistochemical studies of surgical materials from human uterine cervix showed that Mcm3 and 4 are ubiquitously expressed in cancer cells. Further, the positive rate and level of Mcm3 and 4 expression appeared to be higher in cancer cells than in normal proliferating cells of the uterine cervix and dysplastic cells, suggesting that they can be useful markers to distinguish these cells.     

Acantholytic cells exfoliated from pemphigus vulgaris of the uterine cervix. A case report

BACKGROUND: Pemphigus vulgaris of the uterine cervix is rare and almost always associated with cutaneous or mucosal lesions elsewhere on the body. Without a history of pemphigus, acantholytic cells in cervical smears may be misdiagnosed as malignant ones. CASE: A 52-year-old female presented with a vaginal discharge, and a routine cervical smear was collected for cytology. The smear displayed atypical cells lying singly and in loose clusters, having vesicular nuclei, a thin nuclear membrane, prominent nucleoli and well-defined cytoplasmic margins. These were labeled atypical glandular cells of undetermined significance, and colposcopic examination and biopsy were advised. On colposcopy vesicular lesions and erosions were noticed on the cervix. The biopsy revealed typical intact as well as denuded suprabasal bullae of pemphigus vulgaris. On reevaluation of the cytologic smear, the cytomorphologic features correlated well with the acantholytic cells of pemphigus. Thorough reexamination of the patient revealed 2 tiny vesicles on the oral mucosa that, on biopsy, confirmed the diagnosis of pemphigus vulgaris. CONCLUSION: Cytopathologists should be aware of the typical cytomorphologic features of pemphigus vulgaris and, in an appropriate clinical setting, should be able to diagnose or at least suspect this entity in even rare sites like the cervix. A false positive diagnosis of malignancy can be avoided if the cytologic findings are judiciously correlated with the history and with clinical and colposcopic examinations.     

Glassy cell carcinoma of the uterine cervix. Cytologic features and expression of estrogen and progesterone receptors

OBJECTIVE: To identify the cytomorphologic features and investigate the expression of estrogen receptor (ER) and progesterone receptor (PR) in glassy cell carcinoma (GCC) of the uterine cervix. STUDY DESIGN: A retrospective analysis of nine GCCs encountered at Korea Cancer Center Hospital between January 1990 and April 1999 was undertaken. The cervical smears were obtained prior to histologic diagnosis of GCC. The cytomorphologic and clinical features were reviewed, and the expression of ER and PR was investigated immunohistochemically on histologic sections. RESULTS: Smears of GCC were hypercellular and remarkably cohesive. The tumor cells were large and characterized by abundant granular cytoplasm, distinct cell membranes and round to polygonal, large nuclei with prominent nucleoli. In the background tumor diathesis and numerous inflammatory cells containing eosinophils were present. The inflammatory cells (mainly eosinophils) were intimately associated with tumor cells to form "granuloepithelial complex." Immunohistochemically, ER was identified in two of the nine cases and PR in one of them. CONCLUSION: Cytology of GCC has characteristic features that differ from those of other carcinomas or atypical reparative cells. Although there are deceptive mimics of GCC, the characteristic cytologic findings should prompt a diagnosis of GCC. ER and PR positivity was found in two cases (22%) and one case (11%), respectively, of GCC, suggesting that this tumor might be hormonally responsive.     

Pseudotumoral tuberculosis of the uterine cervix. Cytologic presentation

The cytologic presentation of a case of pseudotumoral tuberculosis of the uterine cervix is described. The presence in cervicovaginal smears of epithelioid cells arranged in clusters mixed with Langhans' giant cells was highly suggestive of tuberculosis. This diagnosis was confirmed by the detection of acid-fast bacilli in histologic preparations and cultures from biopsy specimens.     

The role of mast cell tryptase in neoangiogenesis of premalignant and malignant lesions of the uterine cervix.

Recently, mast cell tryptase has been identified as another potent proangiogenic factor in tumors, along with fibroblast and vascular endothelial growth factors. Its role has been studied in a number of cancers, including carcinoma of the uterine cervix, with discordant results. Our aim was to study the expression of tryptase and bFGF in mast cells (MCs) during development of neoangiogenesis in premalignant and malignant lesions of the cervix. Biopsy specimens from 21 patients without cancer and from 63 patients with dysplasias and squamous cell carcinomas were used. They were stained with Alcian blue-safranin O (ABSO) and immunostained with specific antibodies against factor VIII, CD105, tryptase, and bFGF. Tryptase-positive mast cells increased with tumor progression and were close to newly formed blood vessels. Vascularization showed a linear increase from dysplasia to invasive cancer. We suggest that MC tryptase may upregulate neoangiogenesis in carcinogenesis of the uterine cervix.     

Immunohistochemical characterization and distribution of Langerhans cells in normal epithelium of the uterine cervix

Langerhans cells (LCs) were shown up in normal cervical tissue obtained from 32 women whose age ranged from 25 to 68 years, using immunohistological methods. LCs were detected in metaplastic and native squamous epithelium of the cervix; they were positive to Dako-LC and OKDR antibodies and those located in the basal-suprabasal epithelial layers were also OKT6-positive. The density of the LCs was higher during the proliferative phase of the menstrual cycle. The investigation into the lymphocytes present in the stroma and in the squamous epithelium showed a population of T-lymphocytes identified as predominantly T-cytotoxic/suppressor cells, sometimes in contact with LCs. The significance of these findings is discussed.     

Identification of cultured cell employing specific substance--with special references of "reserve cells" in uterine cervix

Identification of endocervical "reserve cell", which have been regarded as the origin of squamous cell carcinoma of the uterine cervix, was attempted employing immunohistochemically specific substances. The antigenicity of keratin, squamous cell carcinoma antigen(SCC), epithelial membrane antigen(EMA), tissue polypeptide antigen(TPA), vimentin, secretory component(SC) and placental alkaline phosphatase(PLAP) was investigated in histological preparations as well as cultured cells obtained from primary culture of endocervical tissue. The immunohistochemical findings in histological preparations revealed the following: a strongly positive reaction with TPA, a slightly positive reaction with EMA, a very slightly positive with SCC and PLAP, and a negative reaction with keratin, vimentin and SC. Cultured cells were divided into 4 groups according to their morphological characteristics; among these, small rounded or polygonal cells with a centric single nucleus showed similar immunocytochemical reactions to those of "reserve cells" in histological preparations, indicating that "reserve cell" can be growing in culture. The results obtained suggest that immunohistocytochemical specific substances may be useful to identify cultured cells.