A.‐C. Hellström

Protein expression patterns in primary carcinoma of the vagina

Protein patterns in six samples from primary vaginal cancers, in five from normal vaginal tissue and in five primary cervical cancers, were analysed using two-dimensional polyacrylamide gel electrophoresis (2-DE). Protein expression profile was evaluated by computer-assisted image analysis (PDQUEST) and proteins were subsequently identified using matrix-assisted laser desorption/ionisation mass spectrometry. The aim was to analyse the protein expression profiles using the hierarchical clustering method in vaginal carcinoma and to compare them with the protein pattern in cervical carcinoma in order to find a helpful tool for correct classification and for increased biomedical knowledge. Protein expression data of a distinct set of 33 protein spots were differentially expressed. These differences were statistically significant (Mann–Whitney signed-Ranked Test, P<0.05) between normal tissue, vaginal and cervical cancer. Furthermore, protein profiles of pairs of primary vaginal and cervical cancers were found to be very similar. Some of the protein spots that have so far been identified include Tropomyosin 1, cytokeratin 5, 15 and 17, Apolipoprotein A1, Annexin V, Glutathione-S-transferase. Others are the stress-related proteins, calreticulin, HSP 27 and HSP 70. We conclude that cluster analysis of proteomics data allows accurate discrimination between normal vaginal mucosa, primary vaginal and primary cervical cancer. However, vaginal and cervical carcinomas also appear to be relatively homogeneous in their gene expression, indicating similar carcinogenic pathways. There might, further, be a possibility to identify tumour-specific markers among the proteins that are differentially expressed. The results from this study have to be confirmed by more comprehensive studies in the future.

Carcinoma of the fallopian tube. A clinical and histopathologic review. The Radiumhemmet series

A histopathologic and clinical review of the Radiumhemmet series of primary fallopian tube carcinoma (PFTC) treated from 1923 to 1991 revealed that 128 cases fulfilled the diagnostic criteria for PFTC. These cases were staged according to the new FIGO staging rules for PFTC. Survival was studied with respect to prognostic factors such as age, stage, histologic subgroups, degree of differentiation and mode of treatment. The mean age at diagnosis was 56 years. Seventy-four per cent were found to be in stage Ia–IIa and 26 % in stage III–IV. Forty-five per cent were nulliparous and 22 % had evidence of previous pelvic inflammatory disease. Treatment modalities changed during the studied period. Thirty-three per cent of patients underwent surgery with total abdominal hysterectomy and bilateral salpingo-oophorectomy while 67 % were incompletely operated. A trend towards improvement in results was noticed—however, it was not statistically significant. Among the 14 prognostic variables tested in the multivariate analysis the first in rank were stage (P = 0.001) and degree of differentiation of the tumors (P = 0.070). Patients receiving chemotherapy had superior survival rates compared with those without chemotherapy (P = 0.0006) and patients with cisplatinum-containing chemotherapy did better than those without cisplatin.

Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value

Background:Cytology-based diagnostics of squamous cervical cancer (SCC) precursor lesions is subjective and can be improved by objective markers.Methods:IHC-based analysis of ANXA6, HSP27, peroxiredoxin 2 (PRDX2), NCF2, and tropomyosin 4 (TPM4) during SCC carcinogenesis.Results:Expression of ANXA6, HSP27, PRDX2, and NCF2 in the cytoplasm of dysplastic cells increased from cervical intraepithelial neoplasia 2/3 (CIN2/3) to microinvasive cancer. Invasive SCC showed lower expression of TPM4 than CIN and normal epithelium. CIN2/3 with the highest sensitivity and specificity differed from normal epithelium by cytoplasmic expression of HSP27. Patients with cytoplasmic HSP27 expression in SCC deviating from that observed in normal epithelium had worse relapse-free (P=0.019) and overall (P=0.014) survival. Invasive SCC with the highest sensitivity and specificity differed from normal epithelium by expression of PRDX2 and TPM4 in the cytoplasm, from CIN2/3 by the expression of ANXA6 and TPM4 in the cytoplasm, and from microinvasive SCC by the expression of PRDX2 and ANXA6 in the cytoplasm. The number of sporadic ANXA6+ cells between the atypical cells increased from CIN2/3 to invasive SCC.Conclusion:Detection of expression changes of the proteins ANXA6, HSP27, PRDX2, NCF2, and TPM4 in SCC precursor lesions may aid current cytological and pathological diagnostics and evaluation of prognosis.

DNA-ploidy and mutant p53 overexpression in primary fallopian tube cancer.

Nuclear DNA content and p53 immunoreactivity were determined in 53 cases of primary fallopian tube cancer (PFTC). All tumors showed a distinctly aneuploid DNA distribution pattern, whereas p53 immunoreactivity was observed in 51% of the cases. If the patients were divided into two groups according to survival time, p53 immunoreactivity was present in 40% of the tumors from patients surviving for more than 8 years and in 65% of tumors from patients who died within 2 years. This difference was not statistically significant (P = 0.438). Patient survival was significantly correlated to the clinical stage (FIGO) (P = 0.0009).

Impact of genomic stability on protein expression in endometrioid endometrial cancer

Background:Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established.Methods:Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry.Results:Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70.Conclusion:Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.