Cyclin D1 overexpression in primary hypopharyngeal carcinomas

Abstract

BACKGROUND. Hypopharyngeal squamous cell carcinomas (HPCS) are associated with an extremely poor prognosis. Generally, conventional clinicopathologic factors have only limited value as prognostic factors for this malignancy. It is therefore clinically important to identify new prognostic factors that accurately reflect the biologic aggressiveness of this malignancy. The amplification and overexpression of the cyclin D1 protooncogene have been reported in a variety of malignancies, and are thought to be related to tumor progression. Based on this phenomenon, the authors inimunohistochemically evaluated overexpression of the cyclin D1 gene in 42 cases of primary HPCS. In addition, the immunohistochemical staining of the proliferation marker MIB-1 (Ki-67 antibody) was also performed. METHODS. Formalin fixed, paraffin embedded biopsy specimens obtained prior to treatment were examined. Cyclin D1 and Ki-67 were detected using monoclonal antibodies by means of the streptavidin-biotin method. The relationship between cyclin D1 overexpression and the stage, histologic grade, presence of lymph node metastases, proliferation index, and survival was then statistically analyzed. The correlation between the proliferation index, other clinicopathologic factors, and survival was also evaluated. RESULTS. Twenty-three (54.8%) HPCS specimens showed a 20% or greater immunoreactivity for cyclin D1. Cyclin D1 overexpression was related to cervical lymph node metastases ( P = 0.037) but not to clinical stage, histologic grade, or the proliferation index. Cyclin D1 negative tumors were associated with a significantly better prognosis ( P = 0.0231, particularly in patients who underwent multimodality treatment. Finally, the MIB-1 labeling index showed no correlation with either the clinicopathologic parameters or overall survival. CONCLUSIONS. Based on these findings, cyclin D1 immunohistochemical staining is considered to be useful, not only as a prognostic factor for HPCS, but also as a means of determining the optimum treatment for each individual patient. Conversely, the MIB-1 labeling index appears to have no clinical significance in HPCS.

Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome

“…These findings are in agreement with previous studies reporting that cyclin D1 overexpression is associated with low grade and low stage 9,10,12,29 -31 and is not related with the Ki67 labeling index 12,31 nor with tumor S-phase 29 in urinary bladder cancer. A lack of association between cyclin D1 expression and tumor cell proliferation has been previously reported in breast 32 and head and neck 33 cancer. Taken together with the results of our present study, these observations suggest that cyclin D1 overexpression is not sufficient per se to induce an increased proliferative activity of tumor cells in vivo compared to cyclin D1-negative tumors.…”

Cyclin D1 Polymorphism and Expression in Patients with Squamous Cell Carcinoma of the Head and Neck

“…In contrast previous work has associated up-regulated expression of cyclin D1 with poor outcome in SCCHN. [13][14][15][16] Although it is assumed, that deregulated expression leads to poor outcome directly through increased cellular proliferation of tumor cells, in a recent study cyclin D1 expression in SCCHN tumors has been associated with an increase in apoptosis and cyclin D1-negative tumors were more proliferatively active. 27 Cyclin D1 expression has been associated with good prognosis in non-small cell lung cancer and bladder cancer 24,28 and both good and bad prognosis in studies on breast and cancer.…”

Pin1 overexpression is associated with poor differentiation and survival in oral squamous cell carcinoma

“…Conversely, cyclin D1 antisense oligonucleotides suppress SCC growth in vitro and in vivo, leading to cellular apoptosis (26). Moreover, overexpression of cyclin D1 has been found associated with a more aggressive phenotype and reduced survival in patients with head and neck SCC including tongue cancer (27)(28)(29)(30)(31). However, in OSCC, there were no significant differences in any of the clinical or pathological parameters and overall survival (32).…”