Wayne D. Lancaster

Basaloid squamous cell carcinoma : A distinctive human papilloma virus-related penile neoplasm : A report of 20 cases

Most penile neoplasms are squamous cell carcinomas (SCC), but there are subtypes that show morphologic and possibly etiologic differences. Clinicopathologic features of 20 patients with basaloid carcinoma (BC), an unusual variant of squamous cell carcinoma, are presented. Median age was 52 years, and all tumors were located in the glans, three confined to the perimeatal region. Average tumor size was 3.8 cm. Microscopically, nests of small, basophilic cells with numerous mitosis were present. Human papillomavirus DNA sequences (type 16), using the polymerase chain reaction (PCR), were found in 9 of 11 cases. Differential diagnosis included urethral transitional cell, basal cell, small cell neuroendocrine, and metastatic carcinoma. Factors more significantly associated with regional metastasis and mortality were tumor thickness greater than 10 mm and infiltration of the corpus cavernosum. A comparison with typical squamous cell carcinoma showed basaloid carcinoma to have a higher histologic grade, a deeper invasion of penile anatomic levels, and a higher mortality rate. Of 17 patients observed, 10 were dead of disease (average time, 34 months), one was alive with disease 6 months after diagnosis, and 5 were alive and free of disease (average time, 71 months); the remaining patient died of other causes. Basaloid carcinoma is a distinctive morphologic subtype of squamous cell carcinoma frequently associated with the human papilloma virus.

Immunoperoxidase localization of papillomavirus antigens in cervical dysplasia and vulvar condylomas

Biopsies of 50 cases of cervical dysplasia (46 mild and 4 moderate) and 40 cases of vulvar condyloma acuminata (genital warts) were screened for the presence of papillomavirus antigens by means of a peroxidase-antiperoxidase method having immunospecificity against the genus-specific (common) antigen(s) of the papillomaviruses. With the use of this technique, on formalin-fixed, paraffin-embedded tissue, papillomavirus antigens were detected in cells with cytologic and histologic features of wart virus infection (so-called koilocytotic atypia). Cells showing a positive reaction for papillomavirus antigens were identified in 24 of 50 (48%) cases of cervical dysplasia and in 20 of 40 (50%) cases of vulvar condyloma. The results of this study provide specific confirmation of the presence of papillomavirus antigens in cervical dysplasia and suggest that the papillomavirus may be an important factor in the etiology of this disease.

Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer.

Objectives/Hypothesis: The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma.

Genome based cell population heterogeneity promotes tumorigenicity: The evolutionary mechanism of cancer

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis. The tumorigenicity of each model has been linked to different molecular pathways, and there is no common molecular mechanism shared among them. According to our hypothesis that genome level heterogeneity is a key to cancer evolution, we expect to reveal that the common link of tumorigenicity between these diverse models is elevated genome diversity. Spectral karyotyping (SKY) was used to compare the degree of karyotypic heterogeneity displayed in various sublines of these five models. The cell population diversity was determined by scoring type and frequencies of clonal and non‐clonal chromosome aberrations (CCAs and NCCAs). The tumorigenicity of these models has been separately analyzed. As expected, the highest level of NCCAs was detected coupled with the strongest tumorigenicity among all models analyzed. The karyotypic heterogeneity of both benign hyperplastic lesions and premalignant dysplastic tissues were further analyzed to support this conclusion. This common link between elevated NCCAs and increased tumorigenicity suggests an evolutionary causative relationship between system instability, population diversity, and cancer evolution. This study reconciles the difference between evolutionary and molecular mechanisms of cancer and suggests that NCCAs can serve as a biomarker to monitor the probability of cancer progression. J. Cell. Physiol. 219: 288–300, 2009.

A spectrum of bilateral squamous conjunctival tumors associated with human papillomavirus type 16

Three patients with bilateral tumors presenting as multiple keratinizing and verrucous lesions of the bulbar and tarsal conjunctiva were determined by DNA amplification and hybridization studies to harbor human papillomavirus type 16 (HPV-16). Results of biopsy in two patients showed infiltrating squamous cell carcinoma in one eye and dysplasia or carcinoma in situ in the fellow eye. In the third patient, focal, inflamed, hypertrophic, papillary lesions with pseudoglandular invaginations of the surface epithelium were found in the tarsal conjunctivae of both eyes. These are the first documented cases of bilateral conjunctival tumors associated with human papillomavirus.

Human papillomavirus infection in “young” versus “old” patients with squamous cell carcinoma of the head and neck

Human papillomavirus (HPV) represents a potential risk factor for squamous cell cancer of the head and neck (SCCHN). We evaluated the prevalence of HPV DNA in patients with SCCHN diagnosed at the University of Michigan from 1994–1996.

Human papillomavirus (HPV) transcripts in malignant inverted papilloma are from integrated HPV DNA

Objectives: The objectives of the study were to detect human papillomavirus (HPV) sequences in nasal inverted papilloma (IP) lesions and to determine whether HPV is involved in the progression of IP to sinonasal squamous cell carcinoma (SCC).

Radiation-induced epigenetic DNA methylation modification of radiation-response pathways

DNA methylation can regulate gene expression and has been shown to modulate cancer cell biology and chemotherapy resistance. Therapeutic radiation results in a biological response to counter the subsequent DNA damage and genomic stress in order to avoid cell death. In this study, we analyzed DNA methylation changes at >450,000 loci to determine a potential epigenetic response to ionizing radiation in MDA-MB-231 cells. Cells were irradiated at 2 and 6 Gy and analyzed at 7 time points from 1–72 h. Significantly differentially methylated genes were enriched in gene ontology categories relating to cell cycle, DNA repair, and apoptosis pathways. The degree of differential methylation of these pathways varied with radiation dose and time post-irradiation in a manner consistent with classical biological responses to radiation. A cell cycle arrest was observed 24 h post-irradiation and DNA damage, as measured by γH2AX, resolved at 24 h. In addition, cells showed low levels of apoptosis 2–48 h post-6 Gy and cellular senescence became significant at 72 h post-irradiation. These DNA methylation changes suggest an epigenetic role in the cellular response to radiation.

Human papillomavirus, cervical cancer and women's knowledge

BACKGROUND Human papillomavirus (HPV) is the major risk factor for cervical cancer. METHODS We implemented a retrospective case-series study to discern HPV knowledge accuracy among women diagnosed with and treated for cervical cancer. Cases (n=1174), identified from the Pathology database, were diagnosed and treated for cervical cancer at the same institution. Data were collected using self-administered questionnaires and by reviewing medical records. RESULTS A total of 328 (27.9%) women returned the completed forms. Only 19% of the respondents had identified HPV as the primary risk factor for cervical cancer. Environmental pollutants, radiation exposure, poor dietary habits, excessive physical activity and family history of cervical cancer were listed as risk factors among many others. Multivariate analysis was performed to determine variables that were best associated with HPV knowledge accuracy. Age and education were the two variables that were statistically associated with the outcome. Younger and more educated women who participated in this study were more likely to know about the association between HPV infection and the risk of cervical cancer. CONCLUSIONS Cervical cancer risk factor knowledge, especially knowledge about HPV is low, even among women with the history of cervical cancer. Younger and more educated women are more likely to have HPV and cervical cancer knowledge accuracy. The importance of personal health practices and the focus on health education should be equally emphasized to achieve successful cancer prevention through vaccination.

Nonrandom chromosomal imbalances in human ovarian surface epithelial cells immortalized by HPV16-E6E7 viral oncogenes

We had previously immortalized human ovarian surface epithelial (HOSE) cells using HPV16E6E7 ORFs. In order to identify crucial genetic events involved during cell immortalization, the genomic profile of immortalization of five HOSE cell lines was analyzed by comparative genomic hybridization. Our results showed that chromosomal imbalance was common in HOSE cells after immortalization. The common chromosomal imbalances identified in immortal HOSE cells are: +19q13.1 (5/5 lines), -13q12 approximately qter (4/5 lines), +5q15 approximately q33 (3/5 lines), +20q11.2 approximately q13.2 (3/5 lines) and -22q11.2 approximately qter (3/5 lines). Other chromosomal imbalances, which were detected in two of the five immortal HOSE cell lines, included gains on chromosome 1 and 11q12 approximately q13, and losses on 2p, 4q, 8p, 10p and 11q14 approximately qter. The chromosomal imbalances observed in HOSE cells before immortalization include -8pter approximately p11.2, -11q23 approximately qter, -13q12 approximately qter and +19 which may represent early genetic events during cell immortalization. The genomic profile was examined in one HOSE cell line (HOSE 6-3) at various stages of immortalization. The genomic profiles of HOSE 6-3 cells after crisis were largely stable. A few additional chromosomal imbalances were detected in the immortalized HOSE cells after an extensive culture period including +11pter approximately q23, -15q23 approximately qter, and +17q12 approximately qter. Identification of nonrandom chromosomal imbalance in immortalized HOSE cells may facilitate the identification of specific chromosomes harboring genes involved in the immortalization of human ovarian surface epithelial cells.