Proliferative pattern of head and neck cancer

Edström, Staffan; Gustafsson, Bertil; Stenman, Göran; Lyden, E; Stein, Harald; Westin, Thomas

doi:10.1016/0002-9610(91)90161-6

Cited by 16 publications

(7 citation statements)

References 21 publications

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“…The proliferation marker Ki-67 is widely used to measure the growth fraction of human tumors in situ (Brown and Gatter 1990;Gerdes 1990). In squamous cell carcinomas of the upper aerodigestive tract, expression of Ki-67 has been shown to correlate with proliferation, histological tumor grade, tumor invasion, lymph node status, and expression of the mutated tumor-suppressor gene p53 (Lorz and Meyer-Breiting 1988;Edstrom et al 1991;Girod et al 1993;Zoeller et al 1994;Kosmehl et al 1995;Youssef et al 1995;Kawamura et al 1996). In the present study, we confirmed the positive correlation of Il-2 expression with Ki-67 expression and the histological tumor grade.…”

Section: Discussionsupporting

confidence: 94%

Endogenous IL-2 in Cancer Cells: A Marker of Cellular Proliferation

Reichert

Watkins

Stanson

et al. 1998

J Histochem Cytochem.

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We have previously demonstrated that interleukin-2 (IL-2) receptors, IL-2 protein, and mRNA for IL-2 are present in human carcinomas in vitro and in vivo. Carcinoma cells synchronized in the G2/M-phase of the cell cycle express significantly more intracytoplasmic IL-2 as well as IL-2R-beta and -gamma than tumor cells in the G0/G1-phase. Here we evaluated immunohistologically the cell cycle-dependent distribution of the proliferation-associated Ki-67 antigen and expression of the cytokine IL-2 in four different carcinoma cell lines. In addition, 34 tissue samples from patients with squamous cell carcinomas of the head and neck were simultaneously analyzed for Ki-67 and IL-2 expression and the data were correlated to the histological grade of the tumors. All tumor cell lines were shown to express IL-2 in the Golgi complex. The strongest IL-2 expression was seen in tumor cells undergoing mitosis, identified by double staining with the antibody to Ki-67. In the tumor tissue, the highest level of co-expression of IL-2 and Ki-67 was observed in poorly differentiated carcinomas, with a labeling index (LI) of 67. 2% for IL-2 and 68.8% for Ki-67. Well-differentiated carcinomas showed a significantly lower expression of both proteins (LI 35.0% for IL-2 and 26.5% for Ki-67). The correlation between the labeling indices was statistically significant (r = 0.747; p<0.001). These results demonstrate that IL-2 expression in human carcinoma tissues is strongly associated with cell proliferation and significantly correlates with the histological tumor grade.

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Section: Discussionsupporting

confidence: 94%

Endogenous IL-2 in Cancer Cells: A Marker of Cellular Proliferation

Reichert

Watkins

Stanson

et al. 1998

J Histochem Cytochem.

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“…The kinetic results obtained in our study are similar to those reported in the limited number of in vivo BUDRbased studies published to date [10,11,15], as was the overall percentage of aneuploidy [16][17][18][19][20]. DNA aneuploidy significantly correlated with poor histological differen tiation grading and with nodal involvement but not with tumor dimension.…”

Section: Discussionsupporting

confidence: 79%

Proliferative Characteristics of Head and Neck Tumors

Benazzo¹,

Mevio²,

Occhini³

et al. 1995

ORL

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Cell proliferation of head and neck cancers was studied in 52 patients using in vivo bromodeoxyuridine (BUDR) incorporation. Patients received 250 mg BUDR intravenously several hours prior to biopsy of the tumor tissue. Bivariate flow cytometry was used and enabled us to rapidly obtain DNA ploidy, labelling index (LI), DNA synthesis time (TS) and tumor potential doubling time (Tpot). This method was found to be suitable to obtain complete cytokinetic data in 46/52 (88.5%) patients. The mean BUDR LI was 7.9% (range 2–18%); mean TS was 11.6 h (range 6–28.5 h); mean Tpot was 5.7 days (range 2–30 days). BUDR LI and TS were significantly correlated with histological differentiation grading: G₃ tumors showed higher LI values and shorter TS values than G₁/G₂ tumors. A similar correlation was found between LI or TS and tumor dimensions. Tpot was also significantly lower in larger tumors, such as in those with a higher grading. No significant correlation was found between LI or TS and DNA ploidy (50% of the tumors in our series were DNA aneuploid), while Tpot was found to be 10 days in diploid tumors, compared to only 6.3 days for the aneuploid tumors (p < 0.05). All cases with documented lymph node involvement (N+) showed significantly higher LI, and shorter TS and Tpot values if related to nodal free ones (Tpot = 10 days in N+ patients and 6.3 days in N–– patients; p < 0.05). The results of this study suggest that the method employed is clinically feasible and could be a useful aid in defining the prognosis of head and neck cancer patients. Since cell kinetic information is readily available using this method, it could be incorporated into clinical trials to improve the design of therapeutic strategies for cancer patients.

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“…4A and B ). Based on previous studies reporting the peripheral localization of proliferative cells within HNSCC lobules ( 25 , 26 ), the relative density of Ki-67-labeled nuclei within the HNSCC lobules was evaluated in the present study ( Fig. 4C and D ).…”

Section: Resultsmentioning

confidence: 99%

Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma

et al. 2016

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Glutathione (GSH) is the keystone of the cellular response toward oxidative stress. Elevated GSH content correlates with increased resistance to chemotherapy and radiotherapy of head and neck (HN) tumors. The purpose of the present cross-sectional study was to evaluate whether the expression of glutamate-cysteine ligase (GCL) accounts for the increased GSH availability observed in HN squamous cell carcinoma (SCC). For that purpose, the messenger (m)RNA levels of the modifier (M) and catalytic (C) subunits of GCL and its putative regulators (namely, nuclear factor erythroid 2-related factor 2, heme oxygenase-1 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) were monitored in 35 surgical resections of untreated HNSCC. The localization of GCLM was evaluated using in situ hybridization and immunohistochemistry. GCLM expression was significantly increased in tumor samples, compared with normal mucosa, both at the mRNA and protein level (P=0.029), but the pathway of GCLM activation remains to be elucidated. Protein expression of GCLM was detected in the cytoplasm and nucleus. GCLM and the proliferation marker Ki-67 displayed a similar distribution, being both mainly expressed at the periphery of tumor lobules. The present study reported increased expression of GCL and the rate-limiting enzyme of GSH synthesis, within HNSCC. The nuclear localization of GCLM and the concomitant expression of Ki-67 suggested that the localization of GSH synthesis contributes to the protection against oxidative stress within hotspots of cell proliferation.

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Proliferative pattern of head and neck cancer

Cited by 16 publications

References 21 publications

Endogenous IL-2 in Cancer Cells: A Marker of Cellular Proliferation

Endogenous IL-2 in Cancer Cells: A Marker of Cellular Proliferation

Proliferative Characteristics of Head and Neck Tumors

Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma

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