Jawbone Cavitation Expressed RANTES/CCL5: Case Studies Linking Silent Inflammation in the Jawbone with Epistemology of Breast Cancer.

BACKGROUND: The role of signaling pathways as part of the cell-cell communication within cancer progression becomes a crucial area. Chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted), also known as the chemokine C-C motif ligand 5 (CCL5) (R/C), is a protein on which cancer research focus due to its link with aggressive cancer development. OBJECTIVE: Research on fatty-degenerative osteonecrosis in jawbone (FDOJ) shows striking overexpression of R/C in these areas. Here we try to elucidate a potential link between jawbone-derived R/C and breast cancer (BC) and compare these findings by immunohistochemical staining. METHODS: Thirty-nine FDOJ samples extracted from 39 BC patients and samples from 19 healthy control were analyzed for R/C expression using bead-based Luminex® analysis. R/C levels from 5 BC patients were measured in serum before and after FDOJ surgery. Bone density, histology, R/C expression, and immunohistochemistry were analysed in 4 clinical case studies. The R/C staining of two FDOJ BC patients is compared with the immunohistochemical staining of BC cell preparations. RESULTS: A high overexpression of R/C was seen in all FDOJ samples. R/C levels in serum were statistically downregulated after FDOJ surgery (p=0.0241). DISCUSSION: R/C induced "silent inflammation" in BC is widely discussed in scientific papers along with R/C triggering of different signaling pathways, which might be a key point in the development of BC. CONCLUSION: Hypothesis that FDOJ may serve as a trigger of BC progression through R/C overexpression was set by the authors, who thus inspire clinicians to make aware of FDOJ throughout the dental and medical community in BC cases.

Immunohistological staining of unknown chemokine RANTES/CCL5 expression in jawbone marrow defects-osteoimmunology and disruption of bone remodeling in clinical case studies targeting on predictive preventive personalized medicine.

BACKGROUND: Fatty degenerative osteonecrosis in the medullary spaces of the jawbone (FDOJ) may be identified as a lesser known source of RANTES/CCL5 (R/C) overexpression. The chemokine R/C also interferes with bone metabolism leading to osteolysis in areas affected by FDOJ. Many dental surgeries require functioning repair mechanisms and these may be disrupted by R/C overexpression. OBJECTIVE: To clarify the way in which R/C expression from adipocytes in FDOJ causes a disturbance in osteogenesis and impacts on medullary stem cells by investigating the detection of R/C expression with immunochemical staining. MATERIALS AND METHODS: We examined the tissue samples of 449 patients with FDOJ to assess the level of the chemokine R/C using bead-based Luminex® analysis. In six clinical case studies of FDOJ, we compared bone density, histological findings, R/C expression, and immunohistochemical staining. RESULTS: R/C is overexpressed by up to 30-fold in the 449 FDOJ cases when compared with healthy jawbone samples. The comparison of the six clinical cases consistently shows greatly reduced bone density, (i.e., osteolysis), but varies in terms of the level of agreement across the other three parameters. DISCUSSION: R/C from FDOJ sources may be implicated in several immune responses and considered a key pathogenetic pathway for increased adipogenesis rather than desirable osteogenesis. Adipocytes pathogenetically act via R/C expression in local FDOJ and systemically on the immune system. CONCLUSION: R/C may be regarded as an important trigger for possible pathological developments in the fate of hematopoietic stem cells. FDOJ is not a rigidly uniform process but reflects changing stages of development. The absence of correlating findings should not be interpreted as a misdiagnosis. It seems appropriate to direct further research in the field of "maxillo-mandibular osteoimmunology" focusing on R/C overexpression in FDOJ areas. This may contribute to the development of personalized strategies in preventive medicine.

Evolving patterns in the diagnosis of reactive gastropathy: data from a prospective Central European multicenter study with proposal of a new histologic scoring system.

Histologic examination of gastric biopsies is crucial for determining the cause of gastritis. This prospective multicenter study was undertaken to investigate different histologic parameters arguing in favor or against the diagnosis of reactive gastropathy and to correlate findings with patient's symptoms and endoscopic findings. A total of 1123 individuals aged 15-93 years participated in a prospective multicenter study (histoGERD trial). Diagnosis of Helicobacter gastritis was made following the Updated Sydney System. Diagnosis of reactive gastropathy was based upon Dixon's parameters of foveolar hyperplasia, smooth muscle fibers in the lamina propria and vasodilatation and congestion of mucosal capillaries. Including paucity of acute and chronic inflammatory cells in analysis, a new score with visual analog scales for the diagnosis of reactive gastropathy was developed. All three histologic parameters in favor of the diagnosis of reactive gastropathy were positively associated with the endoscopic diagnosis of gastritis (p < 0.001), yet negatively with Helicobacter infection (p < 0.001). In contrast, presence of acute and chronic inflammatory cells in lamina propria was positively associated with Helicobacter infection (p < 0.001), yet not with the endoscopic diagnosis of gastritis. Our score demonstrated strong association between histologic and endoscopic diagnoses (p < 0.001), yet not with patient's symptoms. In conclusion, our data prove foveolar hyperplasia, smooth muscle fibers and vasodilatation and congestion as key histologic parameters for the diagnosis of reactive gastropathy. The proposed score may enhance the diagnostic accuracy. It should be validated in future studies.

High-grade trichoblastic carcinoma arising in trichoblastoma: a rare adnexal neoplasm often showing metastatic spread.

It has been debated whether malignant transformation of trichoblastoma occurs. The concept was recently forwarded that basal cell carcinoma is as a malignant neoplasm of follicular germinative cells and should be named trichoblastic carcinoma to show its relationship to trichoblastoma. Almost all basal cell carcinomas are low-grade malignant neoplasms and develop metastases only very rarely, and if so, only after very long duration and untreated growth. Only rare basal cell carcinomas arise in trichoblastomas. Up to now there have only been two reports of high-grade trichoblastic carcinoma arising in trichoblastoma, showing systemic metastatic spread and death. We add two further cases of trichoblastic carcinoma with anaplastic nuclei, arising in trichoblastoma. One of the tumors arose in a small nodular trichoblastoma on the right forearm of an 84-year-old male patient. The other one was a trichoblastic carcinoma at the base of a trichoepithelioma on the right thigh of an 87-year-old woman with Brooke-Spiegler syndrome. Our cases emphasize that high-grade trichoblastic carcinoma develops via malignant transformation of trichoblastoma, and is very rare.