It has been suggested that DNA sequence variants of HPV16 contribute to differences in the behavior of individual cervical lesions. To address this question, we have analyzed the association of HPV16 variants with diagnostic severity in 354 HPV16-positive Oklahoman women. HPV16 variant status was determined by PCR amplification and DNA sequencing of the E6 open reading frame. European sequences were identified in 86% of samples and 14% were non-European. Of the 51 nonEuropean cases, 61% were Asian-American, 23% African and 16% were Native American variants. European prototype and related variants were present in comparable numbers (43% each) but the relative proportion of each differed with diagnostic category. In general, the proportion of European variants and non-European variants increased with diagnostic severity while the European prototype decreased. When adjusted for age and race (white, black or Hispanic), the increased risk for carcinoma/severe dysplasia for non-European variants was statistically significant with an odds ratio of 3.8 (1.3-10.7). However, the analogous comparison for the European variants, although also showing increased association with carcinoma/ severe dysplasia, did not reach statistical significance (OR 5 1.6 (95% CI 0.7-3.6). Overall, HPV16 European sequences (both prototype and related variants), were predominant in Oklahoman women including those with cancers. This suggests that while there appear to be differences among the HPV16-variant categories in risk for progression to invasive cancer, all variant categories are associated with the development of invasive cancer. ' UICCKey words: human papillomavirus; cervical carcinogenesis; cervical intraepithelial lesions; HPV variants; cervical neoplasia Intraepithelial lesions and carcinomas of the cervix have been overwhelmingly demonstrated to be associated with human papillomaviruses, with a particularly strong association with HPV16. [1][2][3] However, the fact that only a minority of women infected with HPV16 develop invasive carcinoma suggests that there are as yet undefined factors that affect the biological outcome in the associated lesions. In addition to various host factors, there has been strong interest in the possible role of DNA sequence variation (and hence protein structure/function) in contributing to the biological progression of individual HPV associated lesions. Intratype HPV variants have been defined as showing less than 2% nucleotide variation in the L1 ORF 4 from the original reference or prototype sequence.5 In addition to the L1 sequence changes, the individual variant types have characteristic nucleotide changes in other parts of the viral genome. These have been particularly well characterized for the E6 ORF 6-8 and LCR. 9,10 For HPV16, the E6 sequence changes have been found to accurately assign variant category to individual isolates. 8,11 The first HPV16 sequence 5 identified was from a European woman and was termed ''European prototype''. Studies performed on a worldwide basis have identified sever...

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of reproductive-age and postmenopausal women. We present the first case of UTROSCT with cytogenetic analysis. The tumor occurred in a 34-year-old woman who presented with menorrhagia and a uterine mass. Histologic examination showed tumor with features of sex cord-like epithelium and abundant fibromuscular stroma without an endometrial stromal sarcoma component. The tumor cells expressed cytokeratin, CD99, vimentin, desmin, smooth muscle actin, and estrogen and progesterone receptors. The majority of the cells analyzed by cytogenetic studies showed two balanced chromosomal translocations: t(X;6)(p22.3;q23.1) and t(4;18)(q21.1;q21.3). Several known tumor-related genes (bcl-2, MALT-1, FVT1, SCCA1, SCCA2, and DCC at 18q21; RAP1 at 4q21; and STL at 6q23) and a gonadal-development related gene (H-Y regulator gene at Xp22.3) are located at or near the translocation breakpoints. The tumor cells of sex cord-like elements were strongly and diffusely immunoreactive for bcl-2 antibody. These cytogenetic and immunohistochemical data may suggest potential molecular mechanisms of tumorigenesis of UTROSCT.

Laser-assisted microdissection (LAM) permits the procurement of relatively pure cell populations from histological sections. When applied to the kidney, LAM combined with molecular biological techniques has expanded our understanding of renal biology and pathology. Both frozen and fixed renal tissues can be microdissected. However, sample type and tissue processing can influence the quality of molecular data generated. Data analysis may also be complicated by relative variations in gene expression levels. Importantly, preliminary studies have shown that molecular data obtained following LAM on the kidney can offer new diagnostic and prognostic information. Thus, LAM and molecular markers may eventually become incorporated into the routine kidney biopsy examination.

Molecular methods have been applied widely for the diagnosis of infectious diseases. Beginning with solution hybridization in the early 1990s, multiple methods for nucleic acid hybridization and amplification have been introduced into the laboratory for the identification and characterization of microbial pathogens. This unit contains examples of several basic approaches for microbial detection or characterization in the laboratory. Methods in this chapter include automated nucleic acid extraction, direct detection of microbial pathogens, and characterization of pathogens by DNA sequencing or typing. Any of these methods could be customized for the characterization of bacteria, fungi, parasites, or viruses.

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The COVID-19 pandemic has caused much suffering through disease and death, disruption of daily life, and economic havoc. Global health infrastructure has been challenged, in some cases failing. In the United States, the inability of laboratories to provide adequate testing for the causative pathogen, severe acute respiratory syndrome coronavirus 2, has been the subject of negative press and national debate. Even so, these challenges have prompted pathology practices and clinical labs to change their organizations and operations for the better. The natural positive evolution of the University of Oklahoma Department of Pathology and OU Health Laboratories has been greatly accelerated by the global pandemic. While developing a substantial COVID testing response, our department of pathology and laboratories have evolved a much nimbler organizational structure, established an important research partnership, built a translational research resource, created a significant reference lab capability, and completed many key hires against a national background of hiring freezes and pay cuts. Also, the high visibility of the clinical lab and pathologists during the outbreak has reinforced the value of lab medicine to patient care across our health system. In the midst of significant ongoing changes to the structure and financing of our underlying organizations, high trust among departmental, hospital, health system, and medical school leadership during the pandemic has promoted these positive changes, allowing us to emerge much stronger from this crisis.

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