Einspahr Janine G, Xu Min-Jian, Warneke James, Saboda Kathylynn, Ranger-Moore James, Bozzo Paul, Duckett Laura, Goldman Rayna, Lin Po, Buckmeier Julie, Alberts David S
Department of Medicine, College of Public Health, University of Arizona, Tucson, AZ, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1841-8. doi: 10.1158/1055-9965.EPI-06-0378. Epub 2006 Oct 4.
To explore p53 and proliferating cell nuclear antigen (PCNA) expression and polyamine content as biomarkers in skin cancer chemoprevention trials, we evaluated their expression in early stages of UV-induced squamous cell tumorigenesis.
Biopsies were collected from three groups: 78 subjects with sun damage on forearms, 33 with actinic keratosis (AK) on forearms, and 32 with previous squamous cell carcinoma. Participants with sun damage were randomized to sunscreen or no sunscreen.
We found significant differences in p53 and polyamines in forearms from the sun-damaged group (11.5 +/- 1.2% for p53, 65.5 +/- 1.9 nmol/g for putrescine, and 187.7 +/- 3.3 nmol/g for spermidine) compared with the group with sun damage plus AK (20.9 +/- 2.3% for p53, P = 0.0001; 81.7 +/- 3.9 nmol/g for putrescine, P = 0.0001; 209.4 +/- 8.2 nmol/g for spermidine, P < 0.06). PCNA was not different. When lesion histology was considered, there was a stepwise significant increase in p53 in biopsies without characteristics of AK compared with early AK (P = 0.02) and AK (P = 0.0006) and a similar pattern for PCNA with the only significant difference between early AK and AK. There was a stepwise increase in putrescine and spermidine in normal, sun-damaged forearm, forearm from subjects with AK, and the AK lesion itself (P < 0.0001). No significant differences in p53 or polyamines were seen in 3-month biopsies or, as a result of sunscreen use, although PCNA in the sun-damaged group not using sunscreen decreased significantly.
p53 expression and polyamines in skin were elevated in early stages of skin tumorigenesis and were not affected by sunscreen, adding validity to their use as biomarkers in skin cancer chemoprevention trials.
为了探索p53和增殖细胞核抗原（PCNA）的表达以及多胺含量作为皮肤癌化学预防试验中的生物标志物，我们评估了它们在紫外线诱导的鳞状细胞肿瘤发生早期阶段的表达情况。
从三组中采集活检样本：78名前臂有晒伤的受试者，33名前臂有光化性角化病（AK）的受试者，以及32名曾患鳞状细胞癌的受试者。有晒伤的参与者被随机分为使用防晒霜组和不使用防晒霜组。
我们发现，与晒伤加AK组相比，晒伤组前臂的p53和多胺存在显著差异（p53为11.5±1.2%，腐胺为65.5±1.9 nmol/g，亚精胺为187.7±3.3 nmol/g）（p53为20.9±2.3%，P = 0.0001；腐胺为81.7±3.9 nmol/g，P = 0.0001；亚精胺为209.4±8.2 nmol/g，P < 0.06）。PCNA无差异。当考虑病变组织学时，与早期AK（P = 0.02）和AK（P = 0.0006）相比，无AK特征的活检样本中p53呈逐步显著增加，PCNA也有类似模式，早期AK和AK之间仅有显著差异。正常、晒伤的前臂、患有AK的受试者的前臂以及AK病变本身的腐胺和亚精胺呈逐步增加（P < 0.0001）。在3个月的活检样本中，或者由于使用防晒霜，p53或多胺均未发现显著差异，尽管未使用防晒霜的晒伤组中PCNA显著降低。
皮肤肿瘤发生早期阶段皮肤中的p53表达和多胺水平升高，且不受防晒霜影响，这增加了它们作为皮肤癌化学预防试验生物标志物的有效性。
