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Anal cytology and HPV detection have high sensitivity but low specificity for detecting AIN 2+. HIV-positive men who have sex with men have a high prevalence of AIN 2+ and require high-resolution anoscopy for optimal detection of high-grade anal dysplasia.

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PTEN is a tumor suppressor gene mutated in various advanced human neoplasias, including glioblastomas and prostate, breast, endometrial, and kidney cancers. This tumor suppressor is a lipid phosphatase that negatively regulates cell survival and proliferation mediated by phosphatidylinositol 3-kinase͞protein kinase B signaling. Using the Cre-loxP system, we selectively inactivated Pten in murine tissues in which the MMTV-LTR promoter is active, resulting in hyperproliferation and neoplastic changes in Pten-null skin and prostate. These phenotypes had early onset and were completely penetrant. Abnormalities in Pten mutant skin consisted of mild epidermal hyperplasia, whereas prostates from these mice exhibited high-grade prostatic intraepithelial neoplasia (HGPIN) that frequently progressed to focally invasive cancer. These data demonstrate that Pten is an important physiological regulator of growth in the skin and prostate. Further, the early onset of HGPIN in Pten mutant males is unique to this animal model and implicates PTEN mutations in the initiation of prostate cancer. Consistent with high PTEN mutation rates in human prostate tumors, these data indicate that PTEN is a critical tumor suppressor in this organ.

Infrared emission spectra of gas-phase naphthalene and pyrene have been measured in the range of 3 to 7.5 micrometers with ultraviolet laser desorption-excitation and a spectroscopic technique featuring single-photon counting in the infrared. The spectra were compared with the unidentified infrared emission bands that are observed in many astronomical objects. Marked discrepancies between those observations and the laboratory emission spectra in the wavelengths and relative intensities of principal spectral features led to the conclusion that small neutral unsubstituted polycyclic aromatic hydrocarbons cannot be the carriers of the unidentified infrared emission bands.

The presence of subendometrial linear striations, subendometrial echogenic nodules, or asymmetric myometrial thickness improves the specificity and PPV of US in diagnosing adenomyosis.

9 Among these cancers, PTEN is considered to be a "gatekeeper" in the endometrium.10 PTEN mutations occur in 50 to 80% of endometrial adenocarcinomas. 5,11Furthermore, PTEN alterations are observed in up to 30% of complex atypical hyperplasias, which are considered to be the direct precursor lesions of endometrial adenocarcinomas and even in early lesions that are intermediate between normal endometrium and benign hyperplasias.12 This progressive accumulation of PTEN mutations may contribute to the transition from premalignant to malignant disease. In a study by Mutter et al, 11 computerized morphometric analysis and selective UV irradiation were used to identify and obtain endometrial adenocarcinomas and associated hyperplasias. Mutations of PTEN were shown to occur in 83% of endometrial adenocarcinomas and 55% of hyperplasias. Most of these mutations occurred in only one allele. However, complete loss of PTEN expression, as seen from immunohistochemical analysis, was observed in 61% of tumors and 97% showed at least some degree of diminished expression. 11 These observations suggest that other mechanisms, including the epigenetic regulation of PTEN by differential methylation may contribute to the loss of PTEN expression. 4 Differential methylation is an important epigenetic control mechanism, which has been implicated in the development of a variety of cancers. Research has shown that methylation of promoter regions of normally unmethylated

BACKGROUNDAnal carcinoma incidence is increasing, and is highest among men with human immunodeficiency virus (HIV) infection who have sex with men. Anal carcinoma and anal intraepithelial neoplasia (AIN) are ascertained on tissue histology, but requires invasive procedures. Screening for AIN using anal cytology was suggested. The authors evaluated agreement on cytologic and biopsy specimens from HIV‐positive men undergoing anal carcinoma screening.METHODSOne hundred twenty‐nine HIV‐positive men with a history of anal‐receptive intercourse underwent anal cytology, anoscopy, and biopsy. Four pathologists independently assessed cytology and biopsy specimens and reached consensus for discordant cases.RESULTSEach pathologist evaluated 120 cytology and 155 biopsy specimens. The weighted kappa value for overall agreement was 0.54 (95% confidence interval [CI], 0.49–0.59) for cytology specimens and 0.59 (95%CI, 0.55–0.63) for biopsy specimens. The median kappa values for pairwise agreement among pathologists and for agreement with consensus were, respectively, 0.69 and 0.77 for cytology and 0.66 and 0.75 for biopsy. At least 3 pathologists were in agreement for 92 (76.7%) cytology and 134 (86.5%) biopsy specimens. Reliability for the Bethesda classification system was at least moderate, except for the cytologic category of atypical squamous cells of undetermined significance (kappa = 0.12). Fourteen of 29 (48.3%) cytology specimens and 36 of 47 (76.6%) biopsy specimens with consensus interpretation of high‐grade squamous intraepithelial lesions (HSIL) were interpreted originally as HSIL by ≥ 3 pathologists. The kappa value for agreement with consensus distinguishing HSIL from non‐HSIL ranged from 0.55 to 0.88 for cytology specimens and from 0.76 to 0.94 for biopsy specimens.CONCLUSIONSAgreement for cytologic and biopsy interpretations was generally at least moderate. Nevertheless, these results supported the need for disease indicators with greater reliabililty. Cancer 2005. © 2005 American Cancer Society.