Purpose: Despite promising initial results, recent Phase III trials of the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib ("Iressa"; AstraZeneca, Wilmington, Delaware) in advanced head and neck squamous cell carcinoma (HNSCC) have been equivocal. Cyclin D1, an EGFR target gene, is frequently overexpressed in HNSCC, has been implicated in its pathogenesis, and is strongly associated with poor prognosis in this disease. Therefore, we examined the relationship between deregulated cyclin D1 expression and sensitivity to gefitinib to determine whether this frequently occurring oncogenic change affected the cellular response to gefitinib.Experimental Design: A panel of six EGFR-overexpressing HNSCC cell lines was used to correlate CCND1 gene copy number, cyclin D1 expression, and response to gefitinib. The effect of constitutive overexpression of cyclin D1 was assessed by establishing stably transfected clonal SCC-9 cell lines.Results: Three of six cell lines displayed cyclin D1 amplification and/or overexpression, and these cell lines were resistant to gefitinib. SCC 9 clones overexpressing cyclin D1 continued to proliferate and maintained their S-phase fraction when treated with gefitinib, whereas empty vector control clones and the parental SCC 9 cells were profoundly inhibited and displayed marked reductions in S-phase. The resistance of cyclin D1-overexpressing clones and cyclin D1-amplified cell lines was associated with maintenance of cyclin D1 expression after gefitinib treatment.Conclusions: These data suggest that deregulated cyclin D1 overexpression may be associated with resistance of HNSCC to EGFR inhibitors. Therefore, the role of cyclin D1 as a marker of therapeutic response and its utility as a prognostic marker in HNSCC warrant additional analysis.
ARF staining in z30% of tumor cells) was an independent predictor of improved disease-free survival (DFS; P = 0.002) and overall survival (OS; P = 0.002). This was further enhanced when p14 ARF positivity was cosegregated with positive (z 1%) p16INK4A staining (DFS, P < 0.001; OS, P < 0.001). Patients whose cancers were p14 ARF negative and p53 positive (>50%) had the poorest outcome (DFS, P < 0.001; OS, P < 0.001) of any patient subgroup analyzed.Conclusions: These data show that in patients with SCC of the tongue, combined nuclear and nucleolar expression of p14 ARF protein predicts for improved DFS and OS independent of established prognostic markers.
A 54-year-old woman presented with a 6-month history of a tender and swollen plaque appearing as a panniculitis affecting the left pretibial area. The initial histopathology revealed dermal and subcutaneous inflammation with interstitial histiocytes and mucinosis suggestive of either granuloma annulare or necrobiosis lipoidica. Over the subsequent 6 months the plaque grew progressively, despite treatment with topical corticosteroids under occlusion. Distal to the plaque reduced sensation developed in the limb. Biopsies of the nodular areas now revealed a dense dermal infiltrate of atypical spindle cells within a prominent myxoid stroma and a pleomorphic multinucleated epithelioid cell component. These features were those of an intermediate grade myxofibrosarcoma. This soft-tissue sarcoma may initially masquerade clinically as a panniculitis and a granulomatous process on biopsy as in our patient, leading to a delay in surgical therapy.
SUMMARY Postmenopausal women with frontal recession may represent a diagnostic challenge, as frontal fibrosing alopecia and alopecia areata may be clinically difficult to distinguish. A 53-year-old postmenopausal woman presented with a progressive fronto-temporal marginal alopecia with sparing of her eyebrows. Scalp biopsy of the affected frontal hairline revealed peribulbar lymphocytic inflammation, but no evidence of lichenoid inflammation, perifollicular fibrosis or scarring. Whereas the pathology strongly favoured alopecia areata, the clinical features overlapped with frontal fibrosing alopecia, a variant of lichen planopilaris targeting the frontal scalp. This paper presents an atypical clinical presentation of alopecia areata, which may be mistaken for frontal fibrosing alopecia.
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