Epidermal growth factor receptor pathway mutation and expression profiles in cervical squamous cell carcinoma: therapeutic implications

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.

Prognostic significance and therapeutic implications of PTEN, EGFR and MAPK/ERK in cervical squamous cell carcinoma

“…Our results are close to that of Bumrungthai et al [13] and Kersemaeker et al [19] who observed worse prognosis associated with EGFR overexpression. The results are also similar to that of Adimi et al [12] and Tian et al [17] who stated that high EGFR expression has shown to be involved in poor response to radiotherapy; and significantly related to poor DFS in patients treated with chemo radiation or surgery.…”

“…Noordhuis et al [18] agreed with us; they found a significant correlation between EGFR and ERK staining. This simple linear correlation wasn't detected by Bumrungthai et al [13]. This contradiction may be due to changes in immunohistochemical protocols.…”

“…Immunohistochemical analysis staining intensity was classified mild, moderate, and marked using the following scale: no staining of any cells (0); mild faint staining; moderate intensity staining; and intense staining. EGFR appears as brown membranous and or cytoplasmic staining while ERK1/2 appears as nuclear brown staining [12,13]. Brown cytoplasmic staining less than 30% was negative and more than 30% of the neoplastic cells were considered positive for PTEN [14].…”

Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

“…Our data therefore also suggest a correlation between TP53 mutations and type II carcinoma, but note that this is based on only 3 tumours. No correlation between TP53 and DFS or OS could be demonstrated based on our findings [37, 38]. …”

The relationship between P53 and EGFR expression with development and progression of endometrial cancer

“…However,our results showed no significant toEGFR expression and intensity in endometrial cancer according histological type (P>0.05.Results of [12] found that EGFR expression was lower in type II(34%) compared with type I EC (46%) and reported that EGFR expression positive in 60(46%)cases endometriod out of 130 and 36(36%) cases uterine serous papillary out of 101. [33]explain that EGFR expression was found in 60 (59.4%)cases out of 101 ofsquamous cell carcinoma. Our findings explain clearly, that the development and progression of endometrial cancer did not affected by p53 and EGFR expression; also these results need other confirmations.…”