RELATIONSHIP BETWEEN THE RESULTS OF IMMUNOHISTOCHEMICAL EXAMINATION (PHH3, KI-67) AND POSITRON EMISSION TOMOGRAPHY DATA (SUVMAX) OF OROPHARYNGEAL SQUAMOUS CELL CARCINOMA

Lysak Andrii; Diadyk Olena

doi:10.31435/rsglobal_ws/30092020/7168

Lysak Andrii Graduate Student of the Department of Pathological and Topographic Anatomy, Shupyk National Medical Academy of Postgraduate Education, Pathoanatomical Center of the National Military Medical Clinical Centre of the Main Military Clinical Hospital, Kyiv https://orcid.org/0000-0003-0917-2688
Diadyk Olena Doctor of Medicine, Professor, Head of the Department of Pathological and Topographic Anatomy, Shupyk National Academy of Postgraduate Education, Kyiv

DOI: https://doi.org/10.31435/rsglobal_ws/30092020/7168

Keywords: oropharyngeal squamous cell carcinoma, tumour differentiation, metabolic activity, immunohistochemistry, positron emission tomography

Abstract

The authors established the relationship between the indicators of immunohistochemical examination — proliferation markers (Ki67) and mitotic count (pHH3) with the indicators of positron emission tomography — SUVmax. The identified patterns of cancer cells differentiation and their metabolic activity are promising for the diagnosing and screening of tumours of varying degrees of progression and origin, which will allow forecasting the course of the disease at all stages of diagnostics. The study intends to assess the level of oropharyngeal squamous cell histopathological differentiation by immunohistochemical diagnostic methods, and their metabolic activity using positron emission tomography.
1. Study of the activity of metabolic processes of transformed oropharyngeal cancer cells using positron emission tomography;
2. Determination of tumour proliferative potential by the number of positive stains to Ki-67 (%) and pHH3 by immunohistochemical diagnostic methods;
3. Identification of the relationship between morphological changes of oropharyngeal cancer cells and their metabolic activity.
Materials and methods. We studied 130 samples of squamous cell carcinoma of the oropharyngeal area. We determined the level of metabolic activity — SUVmax — by positron emission tomography (PET) at the preoperative patient treatment stage. In the postoperative period, the proliferation index (Ki67) and the mitotic count (pHH3) were determined by histological and immunohistochemical methods. Upon assessment of the level of differentiation of tumour cells, patients were divided into three groups: Group I - patients having tumour cells in the G1 phase of mitosis (28 patients); Group II — tumour cells in the G2 phase of mitosis (48 patients); Group III — tumour cells in the G3 phase of mitosis (54 patients). We evaluated PET results according to the Maximum Standard Unit Value (SUVmax).
We determined the relationship between morphological changes and metabolic activity of tumour cells by 2- fluoro-[18F]-2-deoxy-D-glucose accumulation and immunohistochemical examination.
Results. We established a statistically significant difference between the groups (p<0.001 according to the Kruskal- Wallis test for all indicators). Thus, with decreasing Me level, the differentiation of SUVmax of tumours significantly (p<0.05) increases, which indicates an increase in the degree of malignancy of tumours. We evaluated the results of immunohistochemical examination by Ki67 and pH3 markers in the study groups. Comparing Ki67 and pHH3, a statistically significant difference was found between the groups (p<0.001 according to the Kruskal- Wallis test for all indicators). Thus, with a decrease in the Me level, the differentiation of Ki67 increases significantly (p<0.05), and an increase in pH3 indicates an increase in the degree of malignancy of tumours. Conclusions. We statistically proved the relationship between Ki67, pH3 and SUVmax in oropharyngeal squamous cell carcinoma. We established the possibility of preoperative forcasting of the level of tumour differentiation and the use of pHH3 immunohistochemical marker as a reliable criterion for assessing the level of tumour differentiation, including hardly diagnosable squamous cell carcinoma.

References

Well, L., Salamon, J., Kaul, M. G., Farschtschi, S., Herrmann, J., Geier, K. I., Hagel, C., Bockhorn, M., Bannas, P., Adam, G., Mautner V. F., Derlin T. (2019) Differentiation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging. Neuro Onco., 21 (4), 508-516.

Liu J. The dualistic origin of human tumors (2018) Semin Cancer Biol., 53, 1-16.

Rudas, M.S., Nasnikov, I.Yu., Matyakin, G.G. (2007) Pozitronno-photon emission computed tomography praktike. Uchebno-metodicheskoe posobie [Positron-Emission Tomography in Clinical Practice. Manual]. Moscow: Central Clinical Hospital UDP RF [in Russian].

Cohen E. E. W., Bell R. B., Bifulco C. B., Burtness B., Gillison M. L., Harrington K. J., Le Q.-T.,

Lee N. Y., Leidner R., Lewis R. L., Licitra L., Hisham M., Mell L.K., Raben A., Sikora A.G., Uppaluri R., Whitworth F., Zandberg D. P., Ferris R.L. (2019) The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer, 7 (1), 184-215.

Jin S., Li D., Wang H., Yin Y. (2013) Registration of PET and CT images based on multiresolution gradient of mutual information demons algorithm for positioning esophageal cancer patients. Journal of applied clinical medical physics, 14, 1, 50-61.

Osipyan, E.O., & Mudunov, A.M. (2017). Computer and Magnetic Resonance Imaging in Assessing the Local Spread of Tumors of the Oral Cavity and Oropharynx as the Main Factor in the Choice of Treatment Tactics (literature review). Opuholi golovy i shei, 7 (4), 53-62. doi: 10.17650/2222-1468-2017-7-4-53-62 [in Russian].

Sun X., Kaufman P. D. Ki-67: more than a proliferation marke. (2018). Chromosoma., 127 (2), 175-186.

Cheng N. M., Fang Y.-H. D., Tsan D.-L., Lee L.-Y., Chang J. T.-C., Wang H.-M., Ng S.-H., Liao C.-T., Yang L.-Y., Yen T.-C. (2018) Heterogeneity and irregularity of pretreatment 18F-fluorodeoxyglucose positron emission tomography improved prognostic stratification of p16-negative high-risk squamous cell carcinoma of the oropharynx. Oral oncology., 78, 156-162.

Mehanna H. McConkey C. C., Rahman J. K., Wong W.-L., Smith A. F., Nutting C., Hartley A.G., Hall P., Hulme C., Patel D. K., Zeidler S.V., Robinson M., Sanghera B., Fresco L., Dunn J. A. (2017) PET-NECK: a multicentre randomised Phase III non-inferiority trial comparing a positron emission tomography– computerised tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer. Health Technology Assessment. 21.17. doi: 10.3310 / hta21170

Majdoub M. (2018). Prognostic value of head and neck tumor proliferative sphericity from 3’-deoxy-3’-[18 F] fluorothymidine positron emission tomography IEEE Transactions on Radiation and Plasma Medical Sciences, 2 (1), 33-40.

Sayan A., Gonen Z. B., Ilankovan V. (2017) Multiple metastases to bone from squamous cell carcinoma of the oropharynx: unusual findings on positron emission tomography-computed tomography. British Journal of Oral and Maxillofacial Surgery., 55 (10), 1044-1045.

Kulikov, E.P., Zakharkina, T.V., Chernitsyn, K.I., Redkin, A.N. Ryzhikh, O.V. (2015). Combined Positron- Emission and Computed Tomography in the Diagnosis of Primary Metastatic Affection of the Lymph Nodes of the Neck. Rossiyskiy onkologicheskiy zhurnal, 20, 4, 6-8 [in Russian].

Disselhorst, J. A., Bezrukov, I., Kolb, A., Parl, C., & Pichler, B. J. (2014). Principles of PET/MR imaging. J Nucl Med, 55(Supplement 2), 2S-10S.

Burkhardt, A., & Morgenroth, K. (2000). Oralpathologie. 3. Mundhöhle, angrenzendes Weichteil-und Knochengewebe (Vol. 3). Springer.

Casali, C., Cucca, M., Rossi, G., Barbieri, F., Iacuzio, L., Bagni, B., & Uliano, M. (2010). The variation of prognostic significance of Maximum Standardized Uptake Value of [18F]-fluoro-2-deoxy-glucose positron emission tomography in different histological subtypes and pathological stages of surgically resected Non- Small Cell Lung Carcinoma. Lung cancer, 69(2), 187-193.

Lell, M., Mantsopoulos, K., Uder, M., & Wuest, W. (2016). Bildgebung der Kopf-Hals-Region. HNO, 64(3), 189-210.

Khudzhebekova, M.M. (2014). The Role of Positron-Emission Tomography with 18F-FDH in Determining the Degree of Malignancy of non-Hodgkin’s Lymphomas. Radiologiya-praktika, (1), 31-37 [in Russian].

Leijenaar, R. T., Nalbantov, G., Carvalho, S., Van Elmpt, W. J., Troost, E. G., Boellaard, R., ... & Lambin, P. (2015). The effect of SUV discretization in quantitative FDG-PET Radiomics: the need for standardized methodology in tumor texture analysis. Scientific reports, 5, 11075.

Nakamura, K., Kodama, J., Okumura, Y., Hongo, A., Kanazawa, S., & Hiramatsu, Y. (2010). The SUVmax of 18F-FDG PET correlates with histological grade in endometrial cancer. International Journal of Gynecological Cancer, 20(1), 110-115.

Konurbaev, T.R. (2014). Effect of Tumor Metabolism on the Standardized Level of Accumulation of Radiopharmaceutical 18F - FDG (SUV) in Positron-Emission and Computed Tomography in Patients with Esophageal and Gastric Cancer. Sovremennye problemy nauki i obrazovaniya, 1. Retrieved from https://www.science-education.ru/ru/article/view?id=11231 (accessed Jun 11 2018) [in Russian].

Cappabianca, S., Porto, A., Petrillo, M., Greco, B., Reginelli, A., Ronza, F., De Rimini, M. L. (2011). Preliminary study on the correlation between grading and histology of solitary pulmonary nodules and contrast enhancement and [18F] fluorodeoxyglucose standardised uptake value after evaluation by dynamic multiphase CT and PET/CT. Journal of clinical pathology, 64(2), 114-119.

Demina, E.A., Leonteva, A.A., Tumyan, G.S., Ryabukhin, Yu.E., Medvedovskaya, E.G., Trofimova, O.P., ... & Kokosadze, N.V. (2017). The Importance of Positron-Emission Tomography in Optimizing the Therapy of the Spread Stages of Hodgkin’s Lymphoma with the Use of the Intensive EACORP-14 Program. Klinicheskaya onkogematologiya. Fundamental'nye issledovaniya i klinicheskaya praktika, 10(2), 150-157. doi: 10.21320/2500-2139-2017-10-2-150-157 [in Russian].

Schimmelpennink M. C. Vorselaars A.D.M., Veltkamp M., Keijsers R.G.M. (2019) Quantification of pulmonary disease activity in sarcoidosis measured with 18F-FDG PET/CT: SUVmax versus total lung glycolysis., EJNMMI Res., 9 (1), 54-61.

Watanabe Y., Kurihara H., Itami J., Sasaki R., Arai Y., Sugimura K. (2017) Relationship between the uptake of 18 F-borono-L-phenylalanine and L-[methyl- 11 C] methionine in head and neck tumors and normal organs. Radiat Oncol., 14 (1), P. 17-24.