The objective of this study was to assess whether the presence of human papillomavirus (HPV) DNA and/or several genotypes of HPV DNA in cervical cancer are correlated with several clinicopathologic parameters of well-defined prognostic significance and whether virologic parameters are predictors of long-term survival in cancer patients. Two hundred twenty three cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the highly sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathologic parameters and survival data. HPV DNA was detected by PCR in 150 of 193 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histologic tumor types, node status, tumor oxygenation, blood vessel invasion, and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox regression analysis (RR 2.856, P < 0.003 resp. RR 3.444, P < 0.0001). In the multivariate analysis, however, HPV DNA status failed to be of prognostic relevance. Exclusively HPV 16 appears to have an independent impact on the overall survival in cervical patients (RR 3.653, P < 0.002). We conclude that the detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors of uterine cervix remains to be investigated in further studies, and the exact mechanisms by which HPV influences the prognosis of cervical cancer patients have to be defined.
The detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors and cancer free pelvic lymph nodes remains to be investigated in further studies. The exact mechanisms by which HPV influence the prognosis of cervical cancer patients have to be defined.
Recent biochemical and morphological investigations have provided evidence for a heterogeneous composition of keratohyalin in human skin. A major component is filaggrin. In interfollicular epidermis the heterogeneity of keratohyalin is not directly visible, whereas in normal ridged skin bicomponent keratohyalin is revealed by electron microscopy. Skin biopsies of ridged and non-ridged skin of normal individuals and patients with autosomal dominant ichthyosis vulgaris (ADI)--characterized by defective keratohyalin synthesis and lack of filaggrin--were investigated by routine transmission electron microscopy and immunogold postembedding techniques using a commercial monoclonal anti-filaggrin antibody. In normal interfollicular epidermis filaggrin labelling was demonstrated on keratohyalin granules and in the lowermost cornified cells, whereas in ADI patients crumbly keratohyalin granules were present that did not show specific labelling for filaggrin. In normal ridged skin only the major (more electron-dense) component reacted with anti-filaggrin, whereas the attached (less electron-dense) component did not react. Ridged skin of ADI patients contained globular keratohyalin that did not react with anti-filaggrin, thus corresponding to the attached keratohyalin component in normal ridged skin. Our results provide a visible counterpart to the recent biochemical investigations of keratohyalin protein heterogeneity and contribute to the understanding of terminal differentiation in human skin and of the defective keratohyalin synthesis in ADI.
PASH is a benign proliferation of stromal myofibroblasts that affects mostly premenopausal women and typically shows estrogen and progesterone receptor expression, allowing speculation regarding a hormonal cause. It usually presents as an incidental finding on a mammogram or as a palpable mass. We present a case of diffuse asymmetrical massive breast enlargement in a premenopausal woman with history of previous multiple PASH excisions for recurrent lesions, caused by multifocal tumorous PASH virtually replacing the breast parenchyma. Immunohistochemistry examination showed no hormone receptor expression. Despite its benign nature, such presentation of PASH is managed with bilateral mastectomy and immediate reconstruction with expanders for cosmetic and comfort reasons, while tumor excision or expectant management is deemed to lead to recurrence and progression. Although a hormonal origin is speculated based on hormone expression studies and typical patient profile, this case showed 0?% estrogen/progesterone expression in the final histology specimen.
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