Biomedical subjects
Publications and source records attributed to C M Fenoglio.
The relationship of adenomatous polyps and hyperplastic polyps to carcinomas of the colon and rectum are discussed. There is a continuum of neoplastic alterations from adenomas to invasive carcinomas, which is defined. Clinically relevant prognostic factors in adenomas containing cancer are evaluated. Degree of differentiation, depth of invasion, and the relative amount of carcinoma are important factors.
We reviewed 65 intraepithelial lesions of the vulva and distal vagina and compared the presence of koilocytosis, abnormal mitoses, and parabasal or basal nuclear enlargement with DNA microspectrophotometric distribution patterns and the presence of human papillomavirus antigen as determined by immunoperoxidase. Abnormal mitoses and cytologically atypical nuclear enlargement were specific predictors of aneuploidy and were reliable for distinguishing vulvar intraepithelial neoplasia (VIN) from condylomas. Koilocytosis was present in 100% of condylomas and 71% of aneuploid (VIN) lesions, but there were qualitative and quantitative differences in the distribution of koilocytic cells in the two classes of lesions. On the basis of these findings, criteria for distinguishing between VIN and condyloma are proposed.
Immunoperoxidase localization of a human papilloma virus structural antigen (HPV) was attempted in 68 intraepithelial lesions of the vulva, 39 of which were analyzed for nuclear DNA content by microspectrophotometry. Overall, 5.9% (4/68) stained positive for HPV. Ninety percent (35/39) of the cases tested were aneuploid, and, of these, 2.8% (1/35) stained positive for HPV. In contrast, 50% (2/4) of the polyploid lesions were positive. Hence DNA microspectrophotometry and immunoperoxidase localization of HPV are useful coparameters for distinguishing wart virus infection (condylomata) from vulvar intraepithelial neoplasia. HPV is detected infrequently within aneuploid lesions, in keeping with the concept that epithelial maturation is required for virion assembly. Whether the HPV genome exists in a nonreplicative state within the aneuploid cell population is unknown.
Recent investigations have established that approximately half of human breast carcinomas contain an immunohistochemically detectable antigen which is cross-reactive with the 52000-dalton major glycoprotein (gp52) of the mouse mammary tumor virus (MMTV). This antigen can be localized in paraffin-embedded sections of routinely fixed tissues using heterologous antibodies to gp52 or MMTV. This report describes two patients with metastatic carcinoma in axillary lymph nodes without any clinical evidence of a primary lesion in the breast or elsewhere. The localization of the gp52-related antigen in paraffin-embedded sections of both metastatic lesions suggested the presence of primary mammary carcinoma. In both instances, this suggestion was ultimately confirmed by the finding of primary lesions in which the gp52-related antigen was also found.
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A 35-year-old white Jewish homosexual man who had undergone surgery and chemotherapy for an embryonal carcinoma of the testis subsequently developed Kaposi's sarcoma. The neoplasm involved the skin as well as visceral tissues. Tissue derived from a biopsy specimen of one of the skin lesions was used in the in situ hybridization technique for the detection of genetic material. Cytomegalovirus messenger RNA was identified in the neoplastic Kaposi cells in the skin. The significance of this finding is discussed.
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Endometrial hyperplasia and carcinoma represent different points in a disease continuum which may be difficult to distinguish using standard histologic criteria. The role of ancillary biochemical, ultrastructural and immunocytochemical techniques in understanding the normal physiologic responses to hormonal stimuli is briefly considered in order to serve as a basis for an analysis of abnormal proliferative states. Not surprisingly, the ultrastructural and biochemical features of hyperplastic and carcinomatous endometria demonstrate a progressive continuum of abnormalities. The role of the immunohistologic detection of CEA, HCG, Casein, and other markers in distinguishing between the various endometrial diseases is discussed. The endometrium represents one of the more spectacular of endocrine target organs in which marked morphologic and ultrastructural changes occur throughout a women's lifetime. Such changes include those accompanying the menarche and the menopause as well as the extensive remodelling which occurs during the reproductive years. During the latter period, the endometrium cyclically proliferates, undergoes secretory differentiation, regresses, degenerates and regenerates. These regularly occurring changes are distinctive and have been described in histological detail, (Noyes et al., 1950, Noyes, 1973, Dallenbach-Hellweg, 1974), as well as ultrastructurally (Cavazos and Lucas, 1973, Ferenczy and Richart, 1974, Ferenczy, 1977). Morphological studies, coupled with advances in knowledge of steroid biochemistry, have confirmed that the cyclic morphological alterations are under the regulatory role of estrogens and progesterone.
Cloned probes of herpes simplex virus type 2 DNA were used in cytological hybridization experiments to detect herpesvirus RNA transcripts in the neoplastic cells of tumors of the uterine cervix. Virus-specific RNA was shown to represent transcription of limited regions of the genome, of which one is known to code for a DNA-binding protein that can be found by immunoperoxidase staining in the neoplastic cells of these tumors and has also been detected in cells transformed in vitro by this virus.
Human paravertebral ganglia were examined for the presence of specific sequences of viral RNA by in situ cytological hybridization, using as probes individual fragments of herpes simplex virus type 2 DNA. Ganglia were obtained at autopsy from 40 patients, and 14 were positive for herpes simplex virus RNA. Transcripts from the left-hand 30% of the viral genome were detected in all of the herpes simplex virus-positive cases. RNA homologous to other sequences from the L component were present less frequently, and no RNA from the S component was detected. These results argue that specific transcription of the herpes simplex virus genome occurs in latently infected human ganglion cells.
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Four hundred eighty-eight lesions from 456 patients were surveyed for the production of hCG using the immunoperoxidase technique. HCG immunoreactivity was found in 9.1% of the total number of cases studied. The 10% of ovarian cancers expressing hCG included serous, endometrioid, and germ cell tumors. Eighteen point nine percent of neoplastic cervices were positive for hCG; the highest rate of expression was in invasive cancers. Eighteen point nine percent of endometrial cancers were hCG positive; poorly differentiated tumors had the highest percent of marker expression. The significance of "ectopic" hCG expression in nontrophoblastic gynecologic neoplasms is discussed.
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The pathologic and clinical aspects of 21 cases of pure, clear cell carcinoma of the ovary are discussed. The literature is reviewed with particular reference to histogenesis and to the problems related to defining this tumor as a separate clinicopathologic entity. It is suggested that clear cell carcinoma represents a histologic variant of endometrioid carcinoma rather than constituting a separate entity.
Transitional epithelium from 30 cases, including transitional cell carcinoma of various grades and stages, carcinoma in situ, cystitis cystica, and glandularis, as well as normal bladder epithelium, was studied for carcinoembryonic antigen (CEA) content by the immunoperoxidase technique. The results indicate that CEA is present in normal transitional epithelium and that its level frequently decreases in transitional cell carcinoma. These results are related to the findings in studies of urinary CEA excretion.
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Human and murine lymphoid cell populations were induced to express terminal deoxynucleotidyl transferase, a marker of early lymphoid differentiation, by exposure to allogeneic or syngeneic epidermal cells. Control growth medium, fibroblasts, or a mammary epithelial cell line did not induce this marker. These findings suggest that epidermal cells can induce lymphoid cell differentiation in vitro.