Increased phosphorylation of p70 S6 kinase is associated with HPV16 infection in cervical cancer and esophageal cancer

Esophageal cancer (EC) is responsible for almost half a million deaths worldwide annually and has a multifactorial etiology, which may account for its geographical variation in incidence. In the last 30 years the potential of human papillomaviruses (HPV) as oncogenes or co-factors in the tumorigenic process of esophageal squamous cell carcinoma (ESCC) has been widely studied. While the etiology of HPV in cervical and certain other anogenital and aerodigestive cancers has been established, results regarding its role in EC have been largely inconclusive. A causal association can be evaluated only with a case-control study, where normal controls are compared to ESCC cases for the presence of HPV. We reviewed all studies investigating ESCC tissue for HPV DNA and identified 139 that met our inclusion criteria, of which only 22 were case-control studies. Our results support previous findings of higher levels of HPV detection in high-risk ESCC regions than in areas of low risk. In addition, we confirm that the role of HPV in ESCC remains unclear, despite an accumulation of studies on the subject. The variations in investigative technique, study design and sample types tested may account for the lack of consistency in results. There is a need for a meta-analysis of all case-control studies to date, and for large, well-designed case-control studies with adequate power to investigate the association. The potential benefits of prophylactic HPV vaccines could be evaluated if HPV is identified as an etiological factor in EC, highlighting the need for further research in this area.

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“…Thirty‐five studies utilized PCR with HPV detection rates varying widely from 0–94% . Koshiol et al .…”

Section: Hpv In Regions At High‐risk For Esccmentioning

confidence: 99%

Role of human papillomaviruses in esophageal squamous cell carcinoma

Liyanage¹,

Segelov

Garland

et al. 2012

Asia-Pac J Clncl Oncology

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“…The p-AKT and p-p70S6K stainings were validated by Western blotting and other studies, as previously described. 29,30 After deparaffinization and rehydration, slides were subjected to heat-induced epitope retrieval in 10 mmol/L citrate buffer (pH 6.0) for p-p70S6K staining or 1 mmol/L EDTA (pH 8.0) for PTEN and p-AKT staining in a hot water bath (95°C) for 20 minutes. Endogenous peroxidase activity was blocked for 15 minutes in 0.3% hydrogen peroxide.…”

Section: Ihc Analysismentioning

confidence: 99%

PTEN, PIK3CA, p-AKT, and p-p70S6K Status

Esteva

Guo

Zhang

et al. 2010

The American Journal of Pathology

263

111

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Phosphatase and tensin homolog (PTEN) is a key modulator of trastuzumab sensitivity in HER2-overexpressing breast cancer. Because PTEN opposes the downstream signaling of phosphoinositide 3-kinase (PI3K) , we investigated the role of PTEN and other components of the PI3K pathway in trastuzumab resistance. We analyzed the status of PTEN , p-AKTSer473 , and p-p70S6K-Thr389 using immunohistochemistry. PIK3CA mutation status was analyzed by direct sequencing. Primary tumor tissue was available from 137 patients with HER2-overexpressing metastatic breast cancer who had received trastuzumabbased chemotherapy. We observed that each of the four biomarkers alone did not significantly correlate with trastuzumab response , whereas PTEN loss alone significantly correlated with shorter survival times (P ‫؍‬ 0.023). PI3K pathway activation , defined as PTEN loss and/or PIK3CA mutation , was associated with a poor response to trastuzumab (P ‫؍‬ 0.047) and a shorter survival time (P ‫؍‬ 0.015). PTEN loss was significantly associated with a poor response to trastuzumab (P ‫؍‬ 0.028) and shorter survival time (P ‫؍‬ 0.008) in patients who had received first-line trastuzumab and in patients with estrogen receptor-(P ‫؍‬ 0.029) and progesterone receptor-negative tumors (P ‫؍‬ 0.033). p-AKT-Ser473 and p-p70S6K-Thr389 each had a limited correlation with trastuzumab response. When these markers were combined with PTEN loss , an increased correlation with patient outcome was observed. In conclusion , PI3K path- Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% to 25% of invasive breast cancers. Patients with HER2-overexpressing tumors experience a shorter time to relapse and shorter overall survival than patients with tumors of normal HER2 levels.

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“…After being treated with 5% normal goat serum in phosphate-buffered saline (PBS)for15mintoblocknon-specificsites,thesectionswereincubated withprimaryrabbitmonoclonalanti-PSCA(1:500),anti-PIWIL1(1:600), andanti-TBX2(1:400)overnightat4ºC.Afterthat,weusedanultrasensitiveSPkit(MaixinBiological,Fuzhou,China)andDAB(diaminobenzidine) as a chromogen. The sections were then counterstained with hematoxylin and mounted with neutral balsam, and then examined by lightmicroscopy.Weseparatelyscoredforstainingintensity(0:nocolor; 1:lightyellow;2:brownishyellow;3:chocolatebrown)andthepercentof positivecells(0:<5%;1:5-25%;2:26-50%;3:51-75%;4:>75%),and the summation of the two gave the final score (-: 0-2; +: 3-4; ++: 5-6; +++:7) [30].…”

Section: Immunohistochemistrymentioning

confidence: 99%

Expression of PSCA, PIWIL1, and TBX2 in Endometrial Adenocarcinoma

Liu

Xiangyang²,

Zhang³

2010

Onkologie

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Background: Endometrial cancer is the 4th most common gynecological cancer. The expression of prostate stem cell antigen (PSCA), piwi-like 1 (PIWIL1), and T-box 2 (TBX2) in endometrial cancer remains to be elucidated. Material and Methods: The expression of PSCA, PIWIL1, and TBX2 was examined using the streptavidin-peroxidase method in 64 endometrial endometrioid adenocarcinoma (EAC) and paired normal endometrium (NE) samples from the Shaanxi Province in China. Results: Positive expression rates of PSCA, PIWIL1, and TBX2 were 75% (48/64), 25% (16/64), and 56% (36/64), respectively in EACs, but 5% (3/64), 6% (4/64), and 2% (1/64), respectively in NEs. The difference was statistically significant (p < 0.05). PSCA was positively correlated with TBX2 (p = 0.003) but not PIWIL1 (p = 0.188). PIWIL1 was positively correlated with TBX2 (p = 0.003). PSCA was positively correlated with age, tumor grade, and lymph node metastasis (p < 0.05). TBX2 had an association with lymph node metastasis (p = 0.014). PIWIL1 was not associated with clinicopathological features (p > 0.05). Conclusions: We report the first analysis of PSCA, PIWIL1, and TBX2 expression in EAC. Our findings suggest that PSCA and TBX2 might be candidate targets for cancer therapy, and have helped us further understand the carcinogenesis of endometrial cancer.

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Increased phosphorylation of p70 S6 kinase is associated with HPV16 infection in cervical cancer and esophageal cancer

Cited by 35 publications

References 34 publications

Role of human papillomaviruses in esophageal squamous cell carcinoma

Role of human papillomaviruses in esophageal squamous cell carcinoma

PTEN, PIK3CA, p-AKT, and p-p70S6K Status

Expression of PSCA, PIWIL1, and TBX2 in Endometrial Adenocarcinoma

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