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K V Shah

Publications and source records attributed to K V Shah.

At least 109 records · Page 6Linked to original sources

Evaluation of histologic, morphometric, and immunohistochemical criteria in the differential diagnosis of small cell carcinomas of the cervix with particular reference to human papillomavirus types 16 and 18.

Clinicopathologic analyses including immunohistochemical, morphometric, virologic, and DNA ploidy studies were performed on seven cases of small cell (undifferentiated) carcinoma (SCC) and 13 cases of small cell squamous carcinoma (SCSC) of the uterine cervix in an attempt to evaluate which criteria are the most useful in identifying aggressive cervical carcinomas composed of small cells. Highly malignant behavior was found to correlate most closely with the histologic pattern of the tumor. Diffuse infiltration by round to spindle-shaped cells with hyperchromatic nuclei similar to small cell carcinoma in other organs correlated with a high frequency of lymph node metastasis and tumor recurrence. In contrast, tumors with well-defined nests similar to large cell nonkeratinizing squamous cell carcinoma were associated with low rates of lymph node metastasis and recurrence. Although there were trends in the distribution of neuroendocrine and cytokeratin immunohistochemical markers, frequency of detection of HPV 16 and 18 DNA sequences, and ploidy patterns, these features showed considerable overlap and none assisted in consistently separating these two types of neoplasms. Consideration of several features, however, could assist in the differential diagnosis. Women with SCC tended to be younger (mean age 36 yr) compared to women with SCSC (mean age 50 yr). A squamous intraepithelial lesion, i.e., cervical intraepithelial neoplasia, was present in association with 60% of SCSC but was not found in any case of SCC. Tumors positive for keratin and negative for neuroendocrine markers were invariably SCSC, whereas those negative for keratin and positive for neuroendocrine markers were always SCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of peroxidase-labeled DNA probes with radioactive RNA probes for detection of human papillomaviruses by in situ hybridization in paraffin sections.

A study comparing in situ hybridization using nonradioactive DNA probes directly conjugated with horseradish peroxidase (HRP), and 35S-labeled antisense RNA probes for human papillomavirus (HPV) types 6/11, 16, and 18 was performed on formalin-fixed, paraffin-embedded tissue from 34 lesions of the cervix and vulva. These lesions included exophytic condylomas and intraepithelial and invasive neoplasms. HPV 6/11 was detected in two of four condylomata acuminata by both in situ techniques. HPV 16 was detected in 13 of 30 cases of intraepithelial and invasive neoplasms by both methods. Discordance between the two methods occurred in two instances. The radiolabeled probe but not the HRP probe detected HPV 16 in one case of cervical intraepithelial neoplasia (CIN 3), whereas the converse occurred in one case of vulvar intraepithelial neoplasia (VIN 3). HPV 18 was not detected in any of the specimens by either method. This study demonstrates that nonradioactive HRP-labeled probes for the detection of specific HPV types are as sensitive as the more laborious and potentially hazardous radioactive probes.

DNA Probes, HPV↗

Progressive multifocal leukoencephalopathy (PML) in AIDS and in the pre-AIDS era. A neuropathological comparison using immunocytochemistry and in situ DNA hybridization for virus detection.

Twenty-five brains with definite, and three brains with possible, progressive multifocal leukoencephalopathy (PML), including six brains of AIDS patients, were studied with special regard to the detection of papovaviruses. Formalin-fixed serial paraffin sections were immunostained with monospecific anti-JC virus (JCV) and genus-specific anti-simian virus (SV) 40 antisera, and hybridized in situ with DNA probes for JCV and SV 40, respectively. Immunocytochemistry (ICC) and in situ hybridization (ISH) were similarly sensitive in detecting virus in classical PML lesions. In all but one definite PML cases at least one method detected virus (96%). Possible PML tissue was never labeled. Labeling patterns were generally similar in ICC and ISH: mainly oligodendroglia and, less frequently, astroglia harbored virus, whereas labeling of neurons and endothelia was absent. Bizarre giant astrocytes were occasionally labeled by ICC and ISH. Burnt-out lesions harbored JCV DNA but not virus antigens. SV 40 DNA was never detectable. PML morphology in AIDS cases did not usually differ from the disease process seen in the pre-AIDS era. However, two AIDS brains presented extremely extended and, in one case, unusually necrotizing PML damage; in the latter case, PML lesions contained large amounts not only of JCV, but also of human immunodeficiency virus (HIV) antigens. We conclude that ICC and ISH are methods of comparable sensitivity for detection of papovavirus in fluorishing PML lesions. In burnt-out PML lesions only ISH may detect virus. The possibility of an exceptional non-JCV (e.g., SV 40) etiology of PML could be neither confirmed nor disproved. In AIDS, massive coinfection by HIV of PML lesions may increase damage to tissue, resulting in unusually extended and necrotizing PML.

Acquired Immunodeficiency Syndrome↗

Investigation of ovarian neoplasia of low malignant potential for human papillomavirus.

Recent in situ hybridization studies have suggested the presence of human papillomavirus type 6 (HPV-6) DNA in ovarian cancer cells. An association between HPV and ovarian neoplasia of low malignant potential (LMP) has not been previously identified. Paraffin-embedded tissue blocks from 24 patients with LMP ovarian tumors were screened for human papillomavirus DNA. The patients ranged in age from 18 to 73 years. Corresponding microscopic slides from each tissue block were reviewed to confirm the histopathologic diagnosis. For identification of HPV genome, deparaffinized sections were subjected to the polymerase chain reaction to achieve amplification of DNAs of HPV types 6, 11, 16, and 18. For each HPV type, a 120-base-pair region of the E6 gene was targeted for amplification. Human papillomaviral DNA was not detected in the tissue specimens subjected to polymerase chain reaction. These results suggest that HPV types 6, 11, 16, and 18 are not likely to play a role in LMP ovarian tumors. These results do not totally exclude possible contributions of other HPV types.

Adolescent↗

Prevalence of human papillomavirus infections in term pregnancy.

The prevalence of human papillomavirus (HPV) infections in the lower genital tracts of pregnant and nonpregnant women was studied. Cervical and vaginal exfoliated cells were obtained during a routine pelvic examination in 45 pregnant women in early labor, and in 44 nonpregnant women. A detailed questionnaire with emphasis on sexual history and sexually transmitted diseases was administered. The two groups of women were comparable with respect to mean age, prior pregnancy experiences, and number of lifetime sexual partners. Compared with pregnant women, the nonpregnant women had a more frequent history of sexually transmitted diseases (61% versus 39%; p = 0.06), and of genital warts (16% versus 0%; p = 0.01). Utilizing Southern transfer and hybridization with 32P-labeled viral DNA probes for HPV types 6, 11, 16, 18, and 31, DNAs extracted from cervicovaginal exfoliated cells were assessed for HPV genomic sequences. HPV genomic sequences were identified in 25% of nonpregnant women compared with 13.5% of term pregnant women. This difference was not statistically significant (p = 0.26). Six HPV isolates identified in pregnant women were distributed as follows: type 6/11, 1; type 16, 1, type 31, 1; and unknown type, 3. Eleven isolates were identified in nonpregnant women and were distributed as follows: type 6/11, 2; type 16, 6; type 18, 2; and type 31, 1. HPV type 6/11, the type responsible for laryngeal papillomatosis of juvenile onset, was identified in 2% of the pregnant population and accounted for only one of six isolates. HPV DNA-positive pregnant and nonpregnant women were predominantly asymptomatic and had normal Papanicolaou smears and normal clinical examinations.

Adolescent↗

Vulvar carcinomas: search for sequences homologous to human papillomavirus and herpes simplex virus DNA.

Ten cases of intraepithelial carcinoma, five with Bowenoid features and five with early invasion, and ten cases of invasive vulvar carcinoma were examined by in situ hybridization and Southern blot analysis using DNA probes for human papillomavirus (HPV) types 6, 11, 16, 18 and 31. HPV DNA was detected in 90% of the intraepithelial cases and in 10% of the invasive cases. All positive cases showed the presence of DNA of HPV type 16. The cases with intraepithelial lesions revealed a strong correlation between the presence of HPV type 16 DNA, cigarette smoking habit, other potential cofactors such as herpes simplex (HSV) DNA sequences and the use of contraceptive drugs, and clinicopathologic features of Bowen's type in situ squamous cell carcinoma. Similar associations were not observed among the cases with invasive disease. While HPV-16 is associated with differentiated Bowenoid type vulvar intraepithelial neoplasia, which appears to be the most common form of early carcinoma of the vulva, the same association was not seen with respect to advanced vulvar invasive squamous cell carcinoma.

Base Sequence↗

Human papillomavirus in women with vulvar intraepithelial neoplasia III.

Untreated cases of vulvar intraepithelial neoplasia (VIN) III may progress to invasive vulvar carcinoma. Tissues from 29 New Zealand women with VIN III were examined for the presence of human papillomavirus (HPV) types 6, 11, 16 and 18 by in situ hybridization and polymerase chain reaction. HPV 16, the only HPV type detected in the lesions, was identified in about half the cases. HPV-positive women were younger than HPV-negative women, and their lesions displayed koilocytosis more often. In four of five cases in which there was a progression to invasive cancer, HPV 16 was detected in both the VIN III and invasive cancer tissue.

Age Factors↗

Human papillomaviruses and the pathogenesis of cervical neoplasia. A study by in situ hybridization.

In a previous topographic study of cervical conization specimens, condylomatous changes were commonly present in direct contact with intraepithelial neoplasia and were always located distal (ectocervical side) to the neoplasia. Viral DNA was detected by in situ hybridization using 35S-labeled nick translated DNA probes in 50 of 70 cases (71%) which had adequate lesions: HPV-16 in 30, HPV-18 in ten, HPV-31 in six, and multiple types in four cases. HPV-6/11 was detected only once, in a multiple infection. As a rule, a positive cervix contained a single virus type, and the same virus type was found in condylomatous and neoplastic areas. The results suggest that the neoplastic process is initiated in the area of condyloma toward the endocervix and, once established, extends proximally toward the cervical canal. Capsid antigen was detected in 19 cases, indicating that a proportion of the high-grade lesions is potentially infectious.

Adult↗

Study of multiple human papillomavirus-related lesions of the lower female genital tract by in situ hybridization.

Twenty-six women with multiple human papillomavirus (HPV)-related lesions of the lower genital tract were investigated by immunohistochemistry for the internal genus-specific capsid antigen of HPV and by DNA-DNA in situ hybridization with 35S-radiolabeled probes for sequences of HPV-6/11, HPV-16, and HPV-18. The vulva was the most frequently affected site in all of these cases; the cervix was the second most frequently affected site. The lesions displayed the features of papillomavirus infection in 14 patients, and there was also histologic evidence of early neoplasia in 12 patients. The mean age of patients with and without neoplasia was 40 and 30 years, respectively. Evidence of HPV association was found in 73% of the vulvar lesions and in 40% of the other synchronous lesions by one or both methods. Viral DNA was found in 67% of patients with neoplasia and in 71% of patients without neoplasia. Eleven of 12 HPV-positive patients with neoplasia revealed the presence of HPV-16 in their tissues by in situ hybridization. On the other hand, 50% of those without neoplasia had HPV-16 DNA, whereas the presence of HPV-6/11 was found in the other 50%. The clinical course of the disease, the distribution of HPV type, and the type of antigen in patients with and without neoplasia suggest that progression to neoplasia was associated with HPV-16. These results stress the practical value of the in situ hybridization method for the identification of those patients with HPV infection who are at risk for progression to malignancy.

Antigens, Viral↗

Human papillomavirus and epithelial ovarian neoplasia.

In contrast to the strong association between human papillomavirus (HPV) and squamous cell carcinoma of the lower female genital tract, no viral DNA had been found in epithelial ovarian carcinoma. Recently, however, R. H. Kaufman, J. Bornstein, A. N. Gordon, E. Adam, A. L. Kaplan, and K. Adler-Storthy [Gynecol. Oncol. 27, 340-349 (1987)] reported the detection of HPV-6 DNA by in situ hybridization in 10 of 12 patients with advanced epithelial ovarian carcinoma. To further investigate the possible association between HPV and epithelial ovarian neoplasia, tumor from 12 patients with epithelial ovarian adenocarcinoma, 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian adenomas was examined for HPV DNA by the Southern hybridization technique. All the tissues were tested under low stringency for HPV-6 and under high stringency for HPV-6, HPV-16, HPV-18, HPV-31, and HPV-35. In addition, all tissues were tested by polymerase chain reaction for the presence of HPV-6 and HPV-11. Of the 12 patients with adenocarcinoma, 5 were poorly differentiated, 4 serous, 1 endometrioid, 1 mucinous, and 1 mixed. The neoplasms were of grades 2-4 with a predominance of stages III and IV (83%). Of the 3 patients with tumors of low malignant potential, all were serous and stage I. Of the 3 patients with adenomas, 1 was mucinous, 1 serous, and 1 Brenner. We were unable to detect HPV-related sequences in any of the specimens. On the basis of these findings, there appears to be no association between HPV and epithelial ovarian neoplasia.

Adenocarcinoma↗

Detection of BK virus and JC virus in urine and brain tissue by the polymerase chain reaction.

DNAs of the human polyomaviruses BK virus (BKV) and JC virus (JCV) were amplified by the polymerase chain reaction (PCR) by using a single pair of 20-base oligonucleotide primers that were complementary to the same regions of both viruses. The sequences flanked by the primers were unique for each virus and could be differentiated by hybridization with 40-base, 32P-labeled oligonucleotide probes or by cleavage with BamHI. The DNA fragments resulting from amplification of BKV and JCV were 176 and 173 nucleotide pairs, respectively. The sensitivities of PCR for amplification of cloned BKV and JCV DNAs were 10 and 100 copies, respectively. Hybridization with the oligonucleotide probes was specific for each virus. A total of 57 urine samples from three groups of subjects were processed by DNA extraction or boiling and were tested by PCR. Urine samples collected from immunosuppressed patients (n = 11) and previously documented to be positive for BKV, JCV, or both were positive by PCR. Ten percent of urine samples from healthy adults (n = 30) that were previously negative for BKV and JCV were positive for one or both viruses by PCR. Urine samples (n = 16) from four seronegative bone marrow transplant recipients were uniformly negative for BKV. JCV was detected in deparaffinized brain tissue from a patient with progressive multifocal leukoencephalopathy. Specific diagnosis of virus in clinical specimens could be made within 1 day of receipt of the specimens. The PCR method is attractive for use in diagnosing polyomavirus infections because of its sensitivity, specificity, and rapid turnaround time.

BK Virus↗

Anal cancer. Microscopic condyloma and tissue demonstration of human papillomavirus capsid antigen and viral DNA.

Sixteen cases of squamous cell carcinoma of the anus, including 4 incidentally discovered in situ lesions, and 3 anal condylomas, were examined for the presence of human papillomavirus (HPV). All in situ tumors and 6 of the invasive tumors were associated with histologic changes typical of condyloma, despite the absence of clinical anogenital warts. Immunohistochemical studies for viral capsid antigen gave positive reactions in two anal warts and in the condylomatous area associated with one invasive tumor. In situ hybridization was accomplished using isotopic DNA probes for HPV 6/11, 16, 18, and 31. Human papillomavirus 6/11 was expressed in the corresponding capsid-positive regions in the two warts and the wart-associated invasive carcinoma. Both HPV 6/11 and HPV 16 were associated with one carcinoma in situ, and HPV 16 was also found within two invasive anal carcinomas, one of which was associated with an extensive vulvar cancer. While these observations do not resolve the "passenger" or direct oncogenic role for HPV in anal carcinoma, the circumstantial evidence is that the oncogenic influence is similar to that accepted for female genital tract cancer.

Adult↗

Squamous papillary neoplasia of the adult upper aerodigestive tract.

Selected papillary squamous tumors of the upper aerodigestive tract (UADT) mucosa in adult patients do not have well-defined histologic criteria and the clinical behavior is poorly understood. To better characterize this spectrum of neoplasms, UADT papillary neoplasms were evaluated by routine histology, determination of cellular DNA content using Feulgen-stained tissue sections, and the typing of human papillomavirus (HPV) by in situ hybridization. Solitary papillomas were studied in two patients; there was no recurrence in either case, both had normal DNA content, and one was typed as HPV-6 while the other was typed as HPV-11. Seven adult patients with recurrent papillomatosis and at least one biopsy with dysplasia/atypia were identified (mean age at diagnosis, 13.3 years; mean age at last contact, 42.7 years). Six of seven patients had abnormal DNA cellular content in foci of epithelial atypia. In all biopsies evaluated, the papillomas of the seven patients were consistently typed as either HPV-6 or HPV-11. Six patients with malignant papillary neoplasms also had abnormal DNA cellular content, but none revealed evidence of HPV type 6, 11, 16, or 18 by in situ hybridization of tissue sections. In many of the recurrent papillomas, the degree of epithelial atypia encountered was pronounced and was commonly misdiagnosed as carcinoma in situ or papillary carcinoma. The aneuploid DNA content of these foci of atypia reflected the abnormal cellular appearance and partially explained the overdiagnosis of malignancy. However, none of the seven patients were treated for malignant disease and none progressed to invasive carcinoma, with an average follow-up period of almost 30 years. We conclude that histologic and cytologic atypia in HPV-containing papillomatosis may be appreciable. The aneuploid DNA content may represent premalignant conditions and the patient may be at an increased risk for the subsequent development of squamous cancer. However, none of the seven patients with recurrent papillomatosis developed any evidence of malignancy. In addition, none of the patients with papillary carcinomas had previous recurrent papillomatosis.

Adult↗

A serological investigation of BK virus and JC virus infections in recipients of renal allografts.

BK virus (BKV) and JC virus (JCV) infections were evaluated in a serological study of 496 renal transplant recipients and their donors. A seropositive donor increased the rate of primary and reactivation infections with BKV and of primary infections with JCV. BKV infection rates were not influenced by the source of the renal allograft (cadaver versus living related donor); however, primary JCV infections occurred more often in recipients of seropositive cadaveric kidneys. Reactivated JCV infections occurred less frequently in patients treated with antilymphocyte preparation. BKV and JCV infections in renal transplant recipients may be caused either by reactivation of the recipient's latent virus or by virus from the donor kidney. These infections are, however, not associated with adverse outcome (death, high serum creatinine level, or loss of renal function) in the recipient in the early post-transplant period.

Antibodies, Viral↗

BK and JC virus infections in recipients of bone marrow transplants.

Fifty-five recipients of bone marrow transplants were monitored prospectively for urinary excretion of BK (BKV) and JC (JCV) viruses and for infections with other viruses. For both BKV and JCV, viruria occurred exclusively in patients who were seropositive at transplantation, a finding indicating that shedding of virus was very likely the result of reactivation. BKV reactivation, which occurred in 26 (55%) of 47 BKV-seropositive patients, was far more common than JCV reactivation, which was detected in only two (7%) of 30 JCV-seropositive patients (P less than .0001). In most patients, BK viruria began two to eight weeks after transplantation and resolved spontaneously after a two- to three-week period. Posttransplantation, there was a temporal pattern in the onsets of infection with the different viruses; herpes simplex virus infections occurred first (mean, 7 d), followed by BKV infections (mean, 33 d) and then cytomegalovirus infections (mean, 51 d). BK viruria was associated with hemorrhagic cystitis.

Antibodies, Viral↗

Evidence of human infection with a rat-associated Hantavirus in Baltimore, Maryland.

Human sera obtained from two sources in Baltimore were tested for antibodies against a Hantavirus by a variety of techniques. Four persons out of 1,788 had hantaviral antibody as demonstrated by immunofluorescent assay, enzyme-linked immunosorbent assay, and neutralizing assay. Neutralizing antibody titrations against three test viruses indicated that infections were caused by a rat-associated virus. Medical histories of two subjects indicated life-long residence in Baltimore and an absence of foreign travel, implicating a local source of infection.

Adolescent↗