Abstract
BackgroundCervical squamous cell carcinoma (CSCC) is a major cause of female mortality worldwide. This study has examined epidermal growth factor receptor (EGFR) pathway markers that represent actionable pharmacological targets.MethodsHPV16 positive CSCCs (n = 105 patients) from Madhya Pradesh, India were screened for KRAS and PIK3CA mutations by PNA-clamp real-time PCR. Immunohistochemistry (IHC) was performed for EGFR, PIK3CA, PTEN, phospho-AKT, phospho-mTOR and phospho-44/42 MAPK (ERK1/2).ResultsKRAS mutations were detected in 0/91 (0%) and PIK3CA mutations in 19/95 (20.0%) informative specimens: exon 9, E542 (n = 3) and E545 (n = 15); exon 20, H1047R (n = 1). PIK3CA mutation detection was associated with older mean patient age [48.2 vs. 56.6 years (P = 0.007)] and with post-menopausal age: 5/45 (11.1%) patients <50 years vs. 14/50 (28.0%) patients ≥50 years (P = 0.045; OR = 3.11). EGFR expression was present in 60/101 (59.4%) CSCCs and was associated with PIK3CA mutation detection (P < 0.05) but not age (P > 0.05). EGFR and phospho-AKT staining showed associations with tumor grade and/or lymph node status (P < 0.05). Significant associations were not found for the other study markers (P > 0.05).ConclusionThese data show that PIK3CA mutation acquisition is related to patient age and EGFR expression. The absence of KRAS mutations supports the potential of anti-EGFR therapies for CSCC treatment. The relatively high PIK3CA mutation rates indicate that PI3K may be a therapeutic target for a significant subset of CSCC patients. Qualitatively distinct IHC staining profiles for the marker panel were noted patient to patient; however, across patients, consistent linear relationships between up- and downstream pathway markers were not observed. Evaluation of the expression status of potential cancer pathway targets may be of value in addition to molecular profiling for choosing among therapeutic options.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0611-0) contains supplementary material, which is available to authorized users.
Highlights
Cervical squamous cell carcinoma (CSCC) is a major cause of female mortality worldwide
PIK3CA mutation detection was associated with older age: wild type mean age 48.2 (SD 13.7, age range 25–90) vs. mutation mean age 56.6 (SD 10.7, age range 45–80), P = 0.007
PIK3CA mutation data in relation to clinical characteristics are summarized in Table 3 and Additional file 1: Table S1
Summary
Cervical squamous cell carcinoma (CSCC) is a major cause of female mortality worldwide. Cervical cancer is the fourth most common and fatal female malignancy worldwide: each year there are an Bumrungthai et al J Transl Med (2015) 13:244. The introduction of national cervical cytology screening programs among more developed countries (MDCs) has greatly reduced disease incidence and mortality rates [3]. LDCs such as India lack the resources and infrastructure to support comprehensive national cervical cytology screening or HPV vaccination programs. Initiatives are in place, it will likely be many years before screening and vaccination are widely accessible to Indian women, especially in rural areas where the majority of cervical cancer related deaths occur [4, 5]. There is a considerable need for cervical cancer treatments that are effective worldwide
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