Inefficient differentiation response to cell cycle stress leads to genomic instability and malignant progression of squamous carcinoma cells.

Squamous cell carcinoma (SCC) or epidermoid cancer is a frequent and aggressive malignancy. However in apparent paradox it retains the squamous differentiation phenotype except for very dysplastic lesions. We have shown that cell cycle stress in normal epidermal keratinocytes triggers a squamous differentiation response involving irreversible mitosis block and polyploidisation. Here we show that cutaneous SCC cells conserve a partial squamous DNA damage-induced differentiation response that allows them to overcome the cell division block. The capacity to divide in spite of drug-induced mitotic stress and DNA damage made well-differentiated SCC cells more genomically instable and more malignant in vivo. Consistently, in a series of human biopsies, non-metastatic SCCs displayed a higher degree of chromosomal alterations and higher expression of the S phase regulator Cyclin E and the DNA damage signal γH2AX than the less aggressive, non-squamous, basal cell carcinomas. However, metastatic SCCs lost the γH2AX signal and Cyclin E, or accumulated cytoplasmic Cyclin E. Conversely, inhibition of endogenous Cyclin E in well-differentiated SCC cells interfered with the squamous phenotype. The results suggest a dual role of cell cycle stress-induced differentiation in squamous cancer: the resulting mitotic blocks would impose, when irreversible, a proliferative barrier, when reversible, a source of genomic instability, thus contributing to malignancy.

Anatomy and MR imaging appearances of synovial plicae of the knee.

Synovial plicae are normal anatomic structures of the knee that sometimes become symptomatic. Magnetic resonance (MR) imaging and MR arthrography are useful tools in the evaluation of synovial plicae and allow differentiation of these entities from other causes of knee pain. At MR imaging, synovial plicae appear as bands of low signal intensity within the high-signal-intensity joint fluid. Gradient-echo T2-weighted and fat-suppressed T2-weighted or proton density-weighted MR images are optimal for the evaluation of plicae. Plica syndrome, the painful impairment of knee function in which the only finding that helps explain the symptoms is the presence of a thickened and fibrotic plica, should be included in the differential diagnosis of internal derangement of the knee. A diffusely thickened synovial plica, perhaps associated with synovitis or erosion of the articular cartilage of the patella or femoral condyle, in a patient with no other significant MR imaging findings suggests the diagnosis of plica syndrome. Once the diagnosis has been made, nonsurgical treatment is preferable initially. Failure of the patient to improve with conservative treatment leaves arthroscopic excision of the pathologic plica as the treatment of choice.