Frequent presence of incomplete HPV16 E7 ORFs in lung carcinomas: memories of viral infection.

BACKGROUND: HPV16 E6/E7 oncoproteins are critical for cervical carcinogenesis. The corresponding oncogenes are also detected in head and neck cancer, but in lung cancer their presence is strongly debated. PCR-based detection protocols amplify different target sequences. OBJECTIVES: To examine the frequency of different length HPV16 E7 segments in lung carcinomas. STUDY DESIGN: We designed four different amplification schemes for the detection of overlapping segments of the HPV16 E7 ORF, all suitable for specific HPV detection in cervical carcinoma. In two schemes, the entire E7 ORF was targeted while in the remaining schemes internal, smaller sequences were targeted. In total, 76 specimens were used; 29 lung carcinoma specimens, 16 non-cancerous lung tissue specimens from the same patients and 31 bronchial washings from different lung cancer patients. RESULTS: Amplification of the entire HPV16 E7 ORF, using two protocols, demonstrated the absence of the specific HPV16 E7 sequences (74 samples either tested negative by the first PCR protocol or false positive by the second, based on sequencing or AvaII or PvuII digestion). However, both schemes targeting smaller E7 segments revealed the frequent presence of HPV16 E7 sequences in lung carcinoma specimens (14/23 positive by either scheme). CONCLUSIONS: HPV16 E7 sequences are frequently observed in lung carcinomas. Decreasing the size of PCR-target sequences increases the detection frequency, possibly indicating the presence of incomplete viral ORFs. Restriction endonuclease analysis is critical for verifying the reliability of the detection of these sequences.

E-cadherin expression during progression of squamous intraepithelial lesions in the uterine cervix.

Alterations of E-cadherin expression in cervical intraepithelial neoplasias and invasive carcinomas of the uterine cervix have been described by some authors but their clinical significance has not yet been clarified. Archival specimens of 27 normal cervical epithelia, 15 atypical cells of undetermined origin (ASCUS), 53 low-grade squamous intraepithelial lesions (LSIL), 19 high-grade squamous intraepithelial lesions (HSIL) and six invasive squamous carcinomas were evaluated for E-cadherin expression. The cytological material was processed using liquid based cytology (ThinPrep technique) and immunostained for E-cadherin. All HPV infections (koilocytes) showed strong cell membranous E-cadherin expression. In HSIL a strong decrease in E-cadherin expression and heterogeneous distribution was noticed. In the relatively small number of squamous cell carcinomas of the cervix studied, a significant decrease or loss in E-cadherin expression, predominantly cytoplasmic, was noted. We concluded that decreased E-cadherin expression appears to be a useful parameter of malignant potential of cervical lesions. E-cadherin immunoexpression could provide an additional criterion in correlation with cyto- and histomorphology and colposcopy to define high grade CIN lesions.

Mammographic changes during postmenopausal hormonal replacement therapy with tibolone.

PURPOSE OF INVESTIGATION: To evaluate mammographic changes in postmenopausal women receiving hormonal replacement therapy (HRT) with tibolone. METHODS: 83 postmenopausal women aged 45-62 received the same dose of tibolone for a period of six months to five years without interruption. The women were examined mammographically every six to 12 months during the observation period. RESULTS: There was a low incidence of breast tenderness. Also, we did not observe any significantly increased mammographic density or neoplasmatic disease of the breast. As far as dysplastic changes are concerned, no remarkable aggravation in the mammographic picture was noted. CONCLUSION: The new synthetic steroid tibolone, in contrast to conventional HRT, rarely causes breast pain. At least short-period tibolone therapy (less than 5 years) has good effects on climacteric disorders and does not cause breast changes (dysplasia or cancer). Our study is on-going.

Image analysis (DNA ploidy) and expression of c-erb B-2 and p53 in imprint smears of breast cancer.

PURPOSE OF INVESTIGATION: To co-evaluate DNA analysis and the expression of c-erb B-2 and p53 oncoproteins with the histologic type and the other known prognostic factors of breast cancer. METHODS: Sixty-five imprint smears from breast surgical specimens were examined by immunocytochemical staining for c-erb B-2 and p53 and routine pap staining. The immunostaining was considered positive for c-erb B-2 if the cancer cells showed specific membrane staining and for p53 specific nuclear staining. In 30 breast carcinoma imprints, DNA ploidy was evaluated by an image analysis technique using a SAMBA 2005 analyser. RESULTS: From the total number of 53 breast carcinomas which were evaluated in our study 25 (47.1%) showed c-erb B-2 immunopositivity, while 16 (30.18%) exhibited p53 positive nuclear immunoreactivity. Ten out of 13 (76.92%) aneuploid breast carcinomas were positive for c-erb B-2 while five out of 13 (38.46%) showed immunopositivity for p53. CONCLUSION: From our findings it seems that detection of c-erb B-2 and p53 expression in samples of breast carcinomas could be an important prognostic factor and may identify patients with more aggressive disease.

Ultrastructural study of foetal and adult mouse renal tissue implanted in testis.

Kidneys of mice foetuses 15, 17, 19 days old, as well as kidneys of mice 1 and 4 weeks old of the pure C3H/SY species, were implanted into the right testis of 40 adult mice 1.5 to 2 months old, of the same species. The animals were sacrificed after 30 and 60 days and the evolution and development of the renal implants within the testis ware studied. The findings in the light as well as in the electron microscope, showed that the renal implants presented the histologic characters of nephroblastoma, which became clearer the more prolonged the time of the implantation was.