Molecular identification, expression and prognostic role of estrogen- and progesterone receptors in head and neck cancer.

The aims of this study were to assess the sex hormone receptor status of head and neck (HNC) cancers. Frozen surgical samples (n = 67) of HNC patients were analyzed. Protein expression of estrogen receptor (ER)alpha, ERbeta and progesterone receptor (PgR) of tumor cells was determined by immunocytochemistry. Data were confirmed at mRNA level by nested-PCR and sequencing. ER and PgR expressions confirmed by PCR analysis were frequent in HNC: 50.7 and 49.3% respectively. Concerning the ER isoforms, ERalpha expression was predominant over ERbeta in both of oral cavity- as well as laryngeal/hypopharyngeal (LH) cancers. The delta3 splice variant of ERalpha was detected at low frequency, while the delta5 splice variant of ERbeta was frequent in HNC. The incidence of functional receptor expression (coexpression of ER and PgR) was relatively frequent also in HNC (27/67, 40.3%) which was independent of the anatomical location of the tumor. Sex hormone receptor expressions did not affect survival of HNC patients, however, in the LH cancer subgroup ER expression was associated with a trend of shortened survival (p = 0.0636, Mantel-Cox generalized savage). ERalpha,beta and PgR expressions are frequent in HNC and may affect the prognosis of the disease, at least in case of LH cancers.

The effect of leukocyte interleukin injection (Multikine) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia: a possible new approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial.

OBJECTIVES/HYPOTHESIS: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection). STUDY DESIGN: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent). METHODS: Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker. RESULTS: Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values. CONCLUSION: The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.

Progression difference between cancers of the larynx and hypopharynx is not due to tumor size and vascularization.

A recent survey of head and neck cancer indicated a sharp difference in survival between cancer of the hypopharynx and cancers formed in other head and neck sites. We have analyzed tumor size relative to clinical stage and vascularization as possible causes for such a difference in a series of 21 patients with cancer of the laryngopharynx (11 glottic and 10 hypopharyngeal). We found that the volume of the smallest cancers of the larynx at stage 2 is significantly larger than the volume of the cancers of the hypopharynx at stage 4 (P < 0.05). Next, we have determined by immunohistochemistry and morphometry the microvessel density, microvessel perimeter, and vascular endothelial growth factor (VEGF) expression of laryngo-hypopharyngeal cancers. Analysis of these data indicates that there is no difference in vascularization and VEGF expression between these two tumor types. These data strongly suggest that the invasive but not the angiogenic phenotype of hypopharyngeal cancer cells could be responsible for the more aggressive biologic behavior of this head and neck cancer subtype.