Associations Between [18F]FDG-PET and Complex Histopathological Parameters Including Tumor Cell Count and Expression of KI 67, EGFR, VEGF, HIF-1α, and p53 in Head and Neck Squamous Cell Carcinoma
- 168 Downloads
Head and neck squamous cell carcinoma (HNSCC) is one of common cancers worldwide. Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) is increasingly used for diagnosing and staging, as well as for monitoring of treatment of HNSCC. PET parameters like maximum and mean standard uptake values (SUVmax, SUVmean) can predict the behavior of HNSCC. The purpose of this study was to analyze possible associations between these PET parameters and clinically relevant histopathological features in patients with HNSCC.
Overall, 22 patients, mean age, 55.2 ± 11.0 years, with different HNSCC were acquired. Low grade (G1/2) tumors were diagnosed in 10 cases (45 %) and high grade (G3) tumor in 12 (55 %) patients. In all cases, whole body PET was performed. For this study, the following specimen stainings were performed: MIB-1 staining (KI 67 expression), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, hypoxia-inducible factor (HIF)-1α, and human papilloma virus (p16 expression). All stained specimens were digitalized and analyzed by using the ImageJ software 1.48v. Spearman’s correlation coefficient (ρ) was used to analyze associations between investigated parameters. P values <0.05 were taken to indicate statistical significance.
P16-negative tumors showed statistically significant higher SUVmax (ρ = 0.006) and SUVmean values (ρ = 0.002) in comparison to p16-positive carcinomas. No significant differences were identified in the analyzed parameters between poorly and moderately/well-differentiated tumors. In overall sample, there were no statistically significant correlations between the [18F]FDG-PET and histopathological parameters. Also, in G1/2 tumors, no significant correlations were identified. In G3 carcinomas, cell count correlated statistical significant with SUVmax (p = 0.580, P = 0.048) and SUVmean (ρ = 0.587, P = 0.045).
Associations between [18F]FDG-PET parameters and different histopathological features in HNSCC depend significantly on tumor grading. In G1/2 carcinomas, there were no significant correlations between [18F]FDG-PET parameters and histopathology. In G3 lesions, SUVmax and SUVmean reflect tumor cellularity.
Key wordsSUV PET HNSCC KI 67 VEGF EGFR HIF-1α p53
AS drafted the manuscript and participated in the design of the study. HJM participated in the design of the study and coordination and participated in the histopathological analyses. AKH performed the histopathological analyses. KW performed the statistical analysis. OS participated in the design of the study and coordination. SP participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Ethics Approval and Consent to Participate
This prospective study was approved by the institutional review board (Ethic Committee of the Medical Faculty, University of Leipzig) and all patients gave written informed consent. All procedures performed in the present study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Consent for Publication
Consent for publication is not applicable for this study.
Availability of Data and Material
Conflict of Interest
The authors declare that they have no conflict of interest.
- 3.Ng SH, Yen TC, Liao CT, Chang JT, Chan SC, Ko SF, Wang HM, Wong HF (2005) 18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: a prospective study of 124 patients with histologic correlation. J Nucl Med 46:1136–1143Google Scholar
- 4.Surov A, Stumpp P, Meyer HJ, Gawlitza M, Höhn AK, Boehm A, Sabri O, Kahn T, Purz S (2016) Simultaneous 18F-FDG-PET/MRI: associations between diffusion, glucose metabolism and histopathological parameters in patients with head and neck squamous cell carcinoma. Oral Oncol 58:14–20CrossRefGoogle Scholar
- 7.Chan SC, Cheng NM, Hsieh CH, Ng SH, Lin CY, Yen TC, Hsu CL, Wan HM, Liao CT, Chang KP, Wang JJ (2017) Multiparametric imaging using 18F-FDG PET/CT heterogeneity parameters and functional MRI techniques: prognostic significance in patients with primary advanced oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiotherapy. Oncotarget 8:62606–62621Google Scholar
- 9.Haerle SK, Huber GF, Hany TF, Ahmad N, Schmid DT (2010) Is there a correlation between 18F-FDG-PET standardized uptake value, T-classification, histological grading and the anatomic subsites in newly diagnosed squamous cell carcinoma of the head and neck? Eur Arch Otorhinolaryngol 267:1635–1640CrossRefGoogle Scholar
- 10.Kendi AT, Corey A, Magliocca KR, Nickleach DC, Galt J, Switchenko JM, el-Deiry MW, Wadsworth JT, Hudgins PA, Saba NF, Schuster DM (2015) 18F-FDG-PET/CT parameters as imaging biomarkers in oral cavity squamous cell carcinoma, is visual analysis of PET and contrast enhanced CT better than the numbers? Eur J Radiol 84:1171–1176CrossRefGoogle Scholar
- 12.Abgral R, Keromnes N, Robin P, le Roux PY, Bourhis D, Palard X, Rousset J, Valette G, Marianowski R, Salaün PY (2014) Prognostic value of volumetric parameters measured by 18F-FDG PET/CT in patients with head and neck squamous cell carcinoma. Eur J Nucl Med Mol Imaging 41:659–667CrossRefGoogle Scholar
- 15.Wong KH, Panek R, Welsh L, Mcquaid D, Dunlop A, Riddell A, Murray I, du Y, Chua S, Koh DM, Bhide S, Nutting C, Oyen WJG, Harrington K, Newbold KL (2016) The predictive value of early assessment after 1 cycle of induction chemotherapy with 18F-FDG PET/CT and diffusion-weighted MRI for response to radical chemoradiotherapy in head and neck squamous cell carcinoma. J Nucl Med 57:1843–1850CrossRefGoogle Scholar
- 18.Grönroos TJ, Lehtiö K, Söderström KO, Kronqvist P, Laine J, Eskola O, Viljanen T, Grénman R, Solin O, Minn H (2014) Hypoxia, blood flow and metabolism in squamous-cell carcinoma of the head and neck: correlations between multiple immunohistochemical parameters and PET. BMC Cancer 14:876CrossRefGoogle Scholar
- 22.Surov A, Caysa H, Wienke A, Spielmann RP, Fiedler E (2015) Correlation between different ADC fractions, cell count, Ki-67, total nucleic areas and average nucleic areas in meningothelial meningiomas. Anticancer Res 35:6841–6846Google Scholar
- 23.Doll CM, Moughan J, Klimowicz A, Ho CK, Kornaga EN, Lees-Miller SP, Ajani JA, Crane CH, Kachnic LA, Okawara GS, Berk LB, Roof KS, Becker MJ, Grisell DL, Ellis RJ, Sperduto PW, Marsa GW, Guha C, Magliocco AM (2017) Significance of co-expression of epidermal growth factor receptor and Ki67 on clinical outcome in patients with anal cancer treated with chemoradiotherapy: an analysis of NRG oncology RTOG 9811. Int J Radiat Oncol Biol Phys 97:554–562CrossRefGoogle Scholar
- 30.Zang J, Li C, Zhao LN, Shi M, Zhou YC, Wang JH, Li X (2013) Prognostic value of vascular endothelial growth factor in patients with head and neck cancer: a meta-analysis. Head Neck 35:1507–1514Google Scholar
- 34.Deron P, Vangestel C, Goethals I, de Potter A, Peeters M, Vermeersch H, van de Wiele C (2011) FDG uptake in primary squamous cellcarcinoma of the head and neck. The relationship between over expression of glucose transporters and hexokinases, tumour proliferation and apoptosis. Nuklearmedizin 50:15–21Google Scholar
- 37.Leifels L, Purz S, Stumpp P, Schob S, Meyer HJ, Kahn T, Sabri O, Surov A (2017) Associations between 18F-FDG-PET, DWI, and DCE parameters in patients with head and neck squamous cell carcinoma depend on tumor grading. Contrast Media Mol Imaging 5369625Google Scholar
- 39.Anneroth G, Hansen LS (1984) A methodologic study of histologic classification and grading of malignancy in oral squamous cell carcinoma. Scand J Dent Res 92:448–468Google Scholar
- 40.Schouten CS, Hakim S, Boellaard R, Bloemena E, Doornaert PA, Witte BI, Braakhuis BJM, Brakenhoff RH, Leemans CR, Hoekstra OS, de Bree R (2016) Interaction of quantitative 18F-FDG-PET-CT imaging parameters and human papillomavirus status in oropharyngeal squamous cell carcinoma. Head Neck 38:529–535CrossRefGoogle Scholar