A Comparative Analysis of Clinical and Molecular Factors with the Stage of Cervical Cancer in a Brazilian Cohort

Abstract

Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor.Objectives1) To analyze the expression of Ki-67, p53 and p16INK4a in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution.MethodsTissue Micro-Arrays (TMA) from patients with invasive cervical cancer (ICC) and controls were analyzed. HPV DNA detection was done by PCR and in situ hybridization. Ki-67, p53 and p16INK4a were analyzed by immunohistochemistry; clinical data was derived from the chart review.ResultsAdvanced tumor stage (III and IV) was strongly associated (p<0.005) with advanced age (>55 years old), with more than four pregnancies and with the lack of formal education. HPV DNA was found in 94.3% of cases with the most prevalent types being HPV16 (67.5%), followed by HPV33 (12.0%) and HPV35 (3.6%). High expression of Ki-67 and p16 was more common in the advanced FIGO stages (p = 0.023). Women with HPV16 tended to be younger (50.9 years; SE 1.9) compared to women with other types (59.9 years; SE 2.8).ConclusionWe found that Ki-67 and p16 expression were independently associated with the tumor stage. We also noted that about 1/3 of the cervical cancers in this Brazilian cohort were not associated with HPV types directly targeted by the current HPV vaccines.

The role of p16 as putative biomarker for cervical neoplasia: A controversial issue?

“…Several studies have reported p16 overexpression in cervical cancer as well as in high grade cervical intraepithelial neoplasia (CIN2-3), [9][10][11] although the clinical importance of these findings remains controversial. A meta-analysis showed that p16 overexpression in cervical cancer specimens appeared to increase overall or disease-free survival rates, indicating a more favorable prognosis.…”

“…Amaro-Filho et al 9 observed p16 overexpression in invasive cervical cancer, with diffuse patterns and strong intensity, when compared to the control samples. Another study in CIN 1 showed that specimens with diffuse p16 immunostaining had higher chances of progression to CIN 2-3.…”

Clinicopathological correlation of invasive squamous cell carcinoma of uterine cervix: A cross-sectional study

“…Early marriage is a risk factor as frank cases with late stage of the disease is noted when the age of marriage was between 15-19 years followed by 20-24 years 8 .Age at the marriage of fewer than 20 years was 49.25% of cases in a study by Afroj et al 9 83% and 17% of cases had first coitus at less than or equal to 20 years and more than 20 years, respectively, in a study by Jain et al 7 . Amaro-Filho SM et al, in their study, states that the advanced stage was also associated with the age of marriage at less than 17 years but not statistically significant (p=0.752) 14 . Cervical carcinoma behaves as a sexually transmitted disease 8 .…”

“…Among cases, 3.8% were nulliparous, and 96.2% were multiparous in a study by Jyothi V et al 6 . Amaro-Filho SM et al, in their study, states that advanced stage (stage III & IV) shows a significant statistical association (p<0.005) with more than four pregnancies 14 . In the present study, parity ranged from 1 to 11, with a mean of 3.6±1.6.…”

“…In a study, Jain DK et al, the illiterates were 97% and with primary education 3% 7 . Amaro-Filho SM et al, in their study, states that advanced stage (stage III & IV) shows the significant statistical association (p<0.005) with no formal education 14 .…”