The epidermal growth factor receptor pathway in relation to pelvic lymph node metastasis and survival in early-stage cervical cancer

Eijsink, Jasper J.H.; Noordhuis, Maartje; Hoor, Klaske A. ten; Kok, Mirjam; Hollema, Harry; Bock, Geertruida H. de; Nijman, Hans W.; Schuuring, Ed; Wisman, G. Bea A.; Zee, Ate G.J. van der

doi:10.1016/j.humpath.2010.04.017

Cited by 24 publications

(23 citation statements)

References 33 publications

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“…There was a positive expression of EGFR correlated with higher grade, high incidence of lymph node metastases, and advanced stage of cancer. These findings are close to that of Eijsink et al [15] who reported that EGFR overexpression was more frequent in advanced cases of CSCC and significantly associated with disease recurrence. The results are also consistent with Li et al [16] who reported that EGFR over-expression was correlated with increased depth of invasion, LN metastasis, and elevated clinical stage.…”

Section: Discussionsupporting

confidence: 92%

“…The present study disclosed that PTEN expression was significantly associated with, smaller tumor size, lower stage, lower grade and negative LN as detected by Eijsink et al [15], who disclosed that loss of PTEN expression is associated with pelvic LN metastasis. The absence of expression of this tumor suppressor protein is consistent with tumor progression.The present results are close to Lee et al [22] who detected that PTEN staining was inversely correlated to grade of differentiation and also with tumor stage.…”

Section: Discussionsupporting

confidence: 76%

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

Mohammed¹,

Atwa²,

Hegazy³

et al. 2018

Am J Res Med Sci

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Introduction: There is a considerable need for cervical cancer treatments. The epidermal growth factor receptor (EGFR) and its pathway molecules affect cervical squamous cell carcinoma (CSCC) regarding its prognosis and anti-cancer therapy. Aims of Study:To investigate the biologic expression of EGFR and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway mediators in CSCCs, by investigating immunohistochemical expressions of EGFR, extracellular signalregulated kinases (ERK1/2) and phosphatase and tensin homolog (PTEN), in a trial to assess their prognostic and survival outcome. Patients and Methods: Immunohistochemical analysis was performed for 35 cervical squamous cell carcinoma specimens to detect three target antigens EGFR, PTEN, and MAPK/ERK1/2. Results: EGFR and MAPK/ERK1/2 staining showed a significant association with each of the following clinical parameters -increased patient age, high tumor stage, grade and positive lymph nodes (LN). They are also associated with relapse and poor patient survival. PTEN showed a significant association with decreased age, small tumor size, low grade, low stage and negative LN, meaning a good prognostic clinical outcome with less relapse. Conclusion: Cervical cancer patients with PTEN expression had good prognosis in contrary to those with EGFR and ERK expressions that had poor prognosis. Treatment directions of CSCC might be of great benefits in the form of an improved clinical outcome with EGFR pathway targeted therapy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 76%

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

Mohammed¹,

Atwa²,

Hegazy³

et al. 2018

Am J Res Med Sci

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“…As a membrane protein, Bcl-2 is overexpressed in cervical cancer tissue. It can prevent apoptosis and prolong the cell life cycle by inhibiting Ca 2+ increases in the cell, closing cell nuclear transportation, and acting as an antioxidant (Saitoh et al, 1999;Eijsink et al, 2010). In this study, the expression rate of Bcl-2 in cervical cancer was significantly higher than in the normal cervix, chronic cervicitis, or CIN tissues.…”

Section: Discussionmentioning

confidence: 50%

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis

Zhou¹,

Wang²

2015

Genet. Mol. Res.

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ABSTRACT. Cervical cancer is associated with abnormal expression of multiple genes. Survivin and Bcl-2 proteins are apoptosis inhibitors. The tumor suppressor gene CD82, which encodes the protein KAI1, is downregulated in cervical cancer, and is associated with differentiation degree. We investigated the expression levels of three proteins and their correlation with metastasis in cervical cancer by comparing them in different cervical lesions. Immunohistochemistry was used to detect their three protein expression levels in the normal cervix, chronic cervicitis, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. The relationships between the protein expression levels and tumor type, clinical stage, tissue differentiation, invasion, and metastasis were analyzed. Survivin and Bcl-2 expression levels in cervical cancer were significantly higher than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). KAI1 expression was markedly lower in cervical cancer than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). There was no statistical difference between the expression levels of the three proteins in CIN and chronic cervicitis, but there were differences in expression between CIN and normal cervical tissues (P < 0.05). Bcl-2 and survivin levels were positively correlated while KAI1 expression was negatively correlated with clinical stage. Survivin and KAI1 expression levels were associated with lymph node metastasis (P < 0.05), and KAI1 expression was positively related with differentiation degree (P < 0.05). Survivin, Bcl-2, and KAI1 are metastasis-related factors in cervical cancer. Overexpression of survivin and Bcl-2, and low expression of KAI1 promotes cervical cancer progress and metastasis.

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“…There was no PTEN expression observed in three of 10 and 0 of 10 PTEN methylation-negative and -positive cases, respectively. The preliminary data from the study by Eijsink et al (27) showed the presence of PTEN gene promoter methylation in four of 19 (21%) cases. No PTEN immunostaining was observed in these four PTEN methylation-positive cases.…”

Section: Discussionmentioning

confidence: 94%

“…Any discrepancies between the data of the PTEN methylation from the high and the low rates may be due to the number of evaluated patients and/or the samples with/without the radiotherapy and/or chemotherapy. The patients in the study by Yang et al (18) received radiotherapy and/or chemotherapy, and the study by Eijsink et al (27) only analyzed 19 cases. Furthermore, the present study showed that the PTEN protein expression in the 102 cervical cancer tissue samples was significantly correlated with the FIGO stage and lymph node metastasis (P<0.05).…”

Section: Discussionmentioning

confidence: 99%

Promoter region methylation and loss of protein expression of PTEN and significance in cervical cancer

Qi¹,

Yang²,

Zhu³

et al. 2014

Biomedical Reports

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Abstract. The genetic basis underlying cervical tumorigenesis and progression are largely unknown. Phosphatase and tensin homologue (PTEN) is a tumor suppressor gene, and genetic changes of PTEN occurs in various types of cancer suggesting that the inactivation of PTEN may play an important role in the pathogenesis of a variety of human malignancies. In the present study, 102 cervical cancer specimens were examined for the expression of the PTEN gene and promoter methylation using methylation-specific-polymerase chain reaction and immunohistochemistry. The PTEN gene mutation was also assessed using PCR single-strand conformational polymorphism. We examined the correlation between PTEN expression and its associated methylation status and the clinical characteristics of cervical cancer. The results showed that there was one case of an A to G point mutation on exon 9 of the PTEN gene in the cervical cancer tissues. This mutation caused the change of aspartic acid to glycine, and the rate of mutation was 1%. The PTEN gene methylation rate of cervical cancer was 62% (63/102) and the rate was associated with the International Federation of Gynecology and Obstetrics stage, cell differentiation, tumor size and lymph node metastasis (P<0.05). The positive rate of PTEN expression was 49% (50/102) in cervical carcinoma and the PTEN expression between stage I-II and III-IV [60 (27/45) vs. 40% (23/57)] was statistically significant (P<0.01). The PTEN gene expression between the metastasis and no lymph node metastasis groups [26 (10/38) vs. 63% (40/64)] was significantly different (P<0.01). The PTEN gene promoter methylation and its protein expression had a significant correlation (P= 0.042). These results suggest that hypermethylation can inactivate the transcription of PTEN and reduce its protein expression. Downregulated PTEN expression is involved in the pathogenesis, invasion and metastasis of cervical cancer, possibly by regulating the balance between apoptosis and proliferation. Therefore, the PTEN expression may be a good marker for the prognosis of cervical cancer.

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The epidermal growth factor receptor pathway in relation to pelvic lymph node metastasis and survival in early-stage cervical cancer

Cited by 24 publications

References 33 publications

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

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

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis

Promoter region methylation and loss of protein expression of PTEN and significance in cervical cancer

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