Relationship of up-regulation of 67-kd laminin receptor to grade of cervical intraepithelial neoplasia and to high-risk HPV types and prognosis in cervical cancer.
OBJECTIVE
To evaluate the 67-kd laminin receptor (67LR) in cervical cancer and its molecular links to oncogenic HPV types.


METHODS
As part of the HPV-PathogenlSS Study, a series of 150 squamous cell carcinomas (SCCs) and 152 carcinoma in situ (CIN) lesions were examined using immunohistochemical staining for LR67 and tested for HPV using polymerase chain reaction (PCR) with 3 primer sets (MY09/11, GP5+/GP6+, SPF). Followup data were available for all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV clearance/persistence after cone treatment.


RESULTS
67LR expression increased in parallel with increasing grade of CIN (p = 0. 0001), with the most dramatic up-regulation upon the transition from CIN 2 to CIN 3 and further to SCC. This increased expression was associated with CIN 3/cancer at OR 17.04 (95% CI 7.28-39.87). The seemingly significant association of 67LR with high-risk HPV (HR-HPV) detection (OR 2.20, 95% CI 1.27-3.80) was due to confounding by the histologic grade (Mantel-Haenszel common OR = 1.118, 95% CI 0.576-2.168). Using performance indicators, 67LR expression was of little value as a marker of HR-HPV type, and it did not predict clearance/persistence of HR-HPV after treatment of CIN. Similarly, 67LR expression was not an independent prognostic factor in cervical cancer.


CONCLUSIONS
In cervical carcinogenesis, both integrin- and nonintegrin-type LRs (67LR) probably have functions complementary to each other, mediating transient early and stable adhesions, respectively. Up-regulated 67LR expression is significantly associated with progression from CIN 2 to CIN 3 as a marker of cell proliferation. 67LR is probably orchestrated by mechanisms independent of HR-HPV oncoproteins, which seem to be more closely associated with integrin-type laminin receptors.
Branca
Margherita
M
Unità Citoistopatologia, Centro Nazionale di, Epidemiologia, Sorveglianza e Promozione della Salute, Rome, Italy.
Giorgi
Colomba
C
Ciotti
Marco
M
Santini
Donatella
D
Di Bonito
Luigi
L
Costa
Silvano
S
Benedetto
Arrigo
A
Bonifacio
Donatella
D
Di Bonito
Paola
P
Paba
Pierluigi
P
Accardi
Luisa
L
Mariani
Luciano
L
Syrjänen
Stina
S
Favalli
Cartesio
C
Syrjänen
Kari
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D017474:Receptors, Laminin / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology* / Q000821:virology
D014408:Biomarkers, Tumor; D007797:Laminin; D017474:Receptors, Laminin