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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Institute for Clinical Science and Technology, CLINTEC, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm SE-14186, Sweden. marta.lomnytska@ki.se
M I
MI
Lomnytska
S
S
Becker
I
I
Bodin
A
A
Olsson
K
K
Hellman
A-C
AC
Hellström
M
M
Mints
U
U
Hellman
G
G
Auer
S
S
Andersson
D017317:Annexin A6 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D018832:Molecular Chaperones; D019255:NADPH Oxidases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D054464:Peroxiredoxins / Q000378:metabolism*; D011379:Prognosis; D012680:Sensitivity and Specificity; D015996:Survival Rate; D046888:Tissue Array Analysis; D014335:Tropomyosin / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000378:metabolism
D017317:Annexin A6; D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C501213:TPM4 protein, human; D014335:Tropomyosin; C086065:PRDX2 protein, human; D054464:Peroxiredoxins; D019255:NADPH Oxidases; C527764:NCF2 protein, human