O-glycan recognition and function in mice and human cancers.

Protein glycosylation represents a nearly ubiquitous post-translational modification, and altered glycosylation can result in clinically significant pathological consequences. Here we focus on O-glycosylation in tumor cells of mice and humans. O-glycans are those linked to serine and threonine (Ser/Thr) residues via N-acetylgalactosamine (GalNAc), which are oligosaccharides that occur widely in glycoproteins, such as those expressed on the surfaces and in secretions of all cell types. The structure and expression of O-glycans are dependent on the cell type and disease state of the cells. There is a great interest in O-glycosylation of tumor cells, as they typically express many altered types of O-glycans compared with untransformed cells. Such altered expression of glycans, quantitatively and/or qualitatively on different glycoproteins, is used as circulating tumor biomarkers, such as CA19-9 and CA-125. Other tumor-associated carbohydrate antigens (TACAs), such as the Tn antigen and sialyl-Tn antigen (STn), are truncated O-glycans commonly expressed by carcinomas on multiple glycoproteins; they contribute to tumor development and serve as potential biomarkers for tumor presence and stage, both in immunohistochemistry and in serum diagnostics. Here we discuss O-glycosylation in murine and human cells with a focus on colorectal, breast, and pancreatic cancers, centering on the structure, function and recognition of O-glycans. There are enormous opportunities to exploit our knowledge of O-glycosylation in tumor cells to develop new diagnostics and therapeutics.

Local recurrence after breast-conserving therapy for phyllodes tumors: A 15-year retrospective review.

There are few data on the long-term outcomes of patients with phyllodes tumors following breast-conserving surgery with or without radiation therapy (RT). We reviewed 69 patients diagnosed from 2000 to 2015 with surgical specimens available for central pathology assessment for outcome in relation to histopathologic subtype, margin width, and utilization of RT. Median follow-up was 63 months (interquartile range, 35-131 months). Forty-eight patients had benign, 13 borderline, and eight malignant phyllodes tumors, with local recurrence rates of 4%, 0%, and 38%, respectively (P ≤ .04 comparing malignant lesions to both benign and borderline lesions). None of the eight patients who received RT suffered a local recurrence. Two of the 26 (8%) patients with benign phyllodes tumors who did not receive RT with margins that were positive or <1 mm had local recurrence, compared to none of 18 patients with margins 1 mm or wider who did not receive RT. The one patient with a malignant phyllodes tumor who did not receive RT with margins that were positive or <1 mm did not locally recur, while both patients with margins 10 mm or wider who did not receive RT had local recurrence. One patient with a malignant phyllodes tumor developed distant recurrence following local recurrence. Phyllodes histologic type and margin width were both associated with the risk of local recurrence following breast-conserving surgery without RT, though the number of events and patients was too small to show these trends were statistically significant.

Identification of Tn antigen O-GalNAc-expressing glycoproteins in human carcinomas using novel anti-Tn recombinant antibodies.

The Tn antigen is a neoantigen abnormally expressed in many human carcinomas and expression correlates with metastasis and poor survival. To explore its biomarker potential, new antibodies are needed that specifically recognize this antigen in tumors. Here we generated two recombinant antibodies to the Tn antigen, Remab6 as a chimeric human IgG1 antibody and ReBaGs6 as a murine IgM antibody and characterized their specificities using multiple biochemical and biological approaches. Both Remab6 and ReBaGs6 recognize clustered Tn structures, but most importantly do not recognize glycoforms of human IgA1 that contain potential cross-reactive Tn antigen structures. In flow cytometry and immunofluorescence analyses, Remab6 recognizes human cancer cell lines expressing the Tn antigen, but not their Tn-negative counterparts. In immunohistochemistry (IHC), Remab6 stains many human cancers in tissue array format but rarely stains normal tissues and then mostly intracellularly. We used these antibodies to identify several unique Tn-containing glycoproteins in Tn-positive Colo205 cells, indicating their utility for glycoproteomics in future biomarker studies. Thus, recombinant Remab6 and ReBaGs6 are useful for biochemical characterization of cancer cells and IHC of tumors and represent promising tools for Tn biomarker discovery independently of recognition of IgA1.

An atypical syphilis presentation.

We present a case of lichenoid secondary syphilis in the genital area in the absence of other cutaneous or systemic manifestations. The patient did not experience an eruption on the palmar or plantar surfaces, which is rare. This case also is unique because of the intense pruritus associated with the genital lesions, a remarkable dissimilarity from typical secondary syphilitic eruptions that tend to be asymptomatic.