Monoclonal antibody 12D11 (MAb 12D11) has been shown to bind histone H1 isolated from human placenta and other tissues but not histone H1 that has been digested with bacterial alkaline phosphatase. We show here that phosphorylation of phosphatase-treated histone H1 with cyclin dependent-kinase (CDK) restores binding by MAb 12D11. We conclude that MAb 12D11 selectively binds histone H1 that has been phosphorylated by CDKs, and we have investigated the use of MAb 12D11 as an immunohistochemical probe of CDK activity in situ. Previous immunofluorescence studies have revealed strong nuclear staining by MAb 12D11 in proliferating cultured cells and the absence of staining in terminally differentiated cells. Immunohistochemical staining of frozen and formalin-fixed, paraffin-embedded sections of benign tissues with MAb 12D11 was nuclear and confined to recognized foci of cell proliferation. In lymphoid germinal centers, MAb 12D11 preferentially stained large lymphoid cells with a relative lack of staining in small cleaved cells, contrasting with a lack of cell size discrimination observed with the monoclonal antibody proliferation probe, MIB-1. Tumor tissues displayed strong albeit heterogeneous staining of malignant cells by MAb 12D11, with little or no staining observed in surrounding nonneoplastic stromal cells. Differential staining by MAb 12D11 of invasive and in situ carcinoma suggest applications in prognostication. MAb 12D11 may also be useful in identification of tumors more likely to respond to therapeutic CDK inhibitors.
A case of an osteogenic desmoplastic melanoma occurring on the sole of the foot of a 60-year-old African American man is described. The tumor measured 4.8 cm in greatest dimension, invaded to a thickness of 2.2 cm and metastasized to four of ten inguinal lymph nodes. The majority of the tumor had a classic desmoplastic phenotype with malignant spindle cells set in a sclerotic and myxoid matrix and foci of lymphocyte aggregation. In other areas, there were thick trabeculae of bone rimmed by malignant epithelioid melanocytes. There was a markedly atypical lentiginous hyperplasia in the overlying epidermis. Imaging showed no continuity with the underlying calcaneus. The tumor was characterized immunohistochemically by S100 positivity. Pathologists should be aware of this diagnosis and should differentiate it from osteosarcoma.
Strongyloides stercoralis colitis is a severe but easily curable disease with a high mortality rate if left untreated. Strongyloidiasis can persist up to several decades and may lead to a chronic colitis similar to that seen in inflammatory bowel disease (IBD), and the two are often confused. Chronic colitis from IBD is associated with an increased risk of colorectal cancer, so it is plausible that chronic colitis from strongyloidiasis may carry a similar risk. Our case report associates chronic Strongyloides colitis and colorectal cancer.
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