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Abstract Background Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. Methods We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. Results At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. Conclusions We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

Purpose: The aim of this investigation was to evaluate whether the placement of medical-grade calcium sulfate hemihydrate (MGCSH) in fresh extraction sockets might affect the quality of newly formed bone and influence crestal bone changes. Materials and Methods: Forty patients who needed maxillary single- tooth extraction followed by implant insertion were enrolled in the study. Alveoli were required to have four remaining intact walls. After tooth extraction, 22 patients received MGCSH in the extraction sockets (test group), and 18 received no grafting material (control group). At the time of extraction and 3 months later (at implant placement surgery), vertical and horizontal socket dimensions were measured. In addition, during implant placement, tissue specimens were harvested for histologic and immunohistochemical evaluations. Comparisons of test and control tissues were performed with the unpaired Student t test. Results: Vertical resorption of the buccal socket walls and reduction of the buccopalatal width were more pronounced at control sites than at MGCSH sites (1.2 mm versus 0.5 mm, and 3.2 mm versus 2.0 mm, respectively). Formation of 100% living trabecular bone with woven and lamellar arrangements was found in both test and control sections. The average trabecular bone area fraction was greater in the grafted specimens than in control specimens (58.8% versus 47.2%). In the test group, the average percentage of lamellar bone increased from 16.4% to 43.6% from the crestal to the apical region and was greater than in unfilled specimens (11.1% coronally, 22.2% apically; P < .0001). Conclusions: MGCSH seems to be effective in accelerating the bone healing process and minimizing alveolar ridge resorption in intact fresh extraction sockets. [ABSTRACT FROM AUTHOR]

Introduction: Nonhemopoietic neoplasms (NHNs) may be encountered during routine flow cytometry (FC) immunophenotyping. The clue of their presence mainly relies on detection of CD45‐negative (CD45−) cells with altered scatter parameters. Methods: In this study, we evaluated a monoclonal antibody combination conceived to characterize the CD45− population by FC, suspected of belonging to NHNs, when present. The panel included CD45 for leucocytes identification, CD326 (clones BerEP4 and HEA‐125) to mark epithelial cells, CD33 to identify myeloid cells, CD138 to trace plasma cells and CD56 useful in the identification of neuroendocrine tumours. 7AAD vital dye was used to gate out dead cells. Results were correlated with cytomorphology and confirmed by histological data, if available. Results: Among 9422 specimens submitted for routine FC investigation, 47 samples that included fine‐needle aspirates, bone marrow aspirates, tissue biopsies and body fluids had a detectable CD45− population and a sufficient cell amount to be further investigated. FC revealed the presence of CD326‐positive epithelial cells in 38 specimens; altered scatter parameters and variable reactivity to the other antigens tested allowed to suspect NHNs in the remaining nine samples. The presence of NHNs was confirmed in all cases by morphology. Conclusions: The current results show that when CD45− cells with altered scatter parameters were detected, cytometrists involved in leukaemia/lymphoma diagnosis may require further FC investigations to rapidly identify NHNs in different specimens, thus reducing the time of the immunohistochemical diagnostic workup to reach a final diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Mutations in the JAK2, CALR, and MPL genes have been shown to have prognostic value in essential thrombocythaemia (ET), but no clear association with morphological changes has been reported so far. We investigated the possible correlation between gene mutations and histopathological features in bone marrow (BM) biopsies of patients with ET. Methods: Marrow cellularity, fibrosis, and the number of total and dysmorphic megakaryocytes and clusters of megakaryocytes were compared to gene mutations in 90 cases of ET at diagnosis. Results: The JAK2V617F mutation was found in 58.9%, CALR in 28.9%, and MPL in 4.4% of the cases, and 7.8% were triple-negative. JAK2V617F-mutated ET showed a high BM cellularity, the lowest number of clusters of megakaryocytes and the highest number of dysmorphic megakaryocytes; CALR-mutated ET showed a reduced BM cellularity, many clusters of large megakaryocytes, and very few dysmorphic megakaryocytes; MPL-mutated ET showed the lowest BM cellularity, the highest number of clustered and large megakaryocytes, and the lowest number of dysmorphic megakaryocytes. Triple-negative ET cases had the highest BM cellularity. Conclusions: Distinct morphological patterns were associated with gene mutations in ET, supporting the classification of ET into different subtypes. [ABSTRACT FROM AUTHOR]

Receptor activator of NFκB ligand (RANKL), RANK, and osteoprotegerin (OPG) represent the key regulators of bone metabolism both in normal and pathological conditions, including bone metastases. To our knowledge, no previous studies investigated and compared RANK expression in primary tumors and in bone metastases from the same patient. We retrospectively examined RANK expression by immunohistochemistry in 74 bone metastases tissues from solid tumors, mostly breast, colorectal, renal, lung, and prostate cancer. For 40 cases, tissue from the corresponding primary tumor was also analyzed. Sixty-six (89%) of the 74 bone metastases were RANK-positive and, among these, 40 (59.5%) showed more than 50% of positive tumor cells. The median percentage of RANK-positive cells was 60% in primary tumors and metastases, without any statistically significant difference between the two groups ( P = 0.194). The same percentage was obtained by considering only cases with availability of samples both from primary and metastasis. Our study shows that RANK is expressed by solid tumors, with high concordance between bone metastasis and corresponding primary tumor. These data highlight the central role of RANK/RANKL/OPG pathway as potential therapeutic target not only in bone metastasis management, but also in the adjuvant setting. J. Cell. Physiol. 226: 780-784, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the transformation of Myelodysplastic syndrome with del (5q) and JAK2 mutation to acute myeloid leukaemia with complex karyotype.

Tissue sections of lymph nodes, appendices and tonsils, together with smears of immunologically separated peripheral lymphoid cells from a B-CLL and lymphomatous cells from an immunocytoma were submitted to combined enzyme cytochemical investigations with acid α-naphthyl acetate esterase (ANAE), β-glucuronidase (B-G), acid phosphatase (AcPh), adenosine triphosphatase (ATPase), a,d 5′ nucleotidase (5′N). T-cells were AcPh +, ATPase- and 5′N -. The vast majority of T- and B-cells displayed ANAE and B-G activities with two distinct staining patterns (T-like and B-like pattern). A high proportion of lymphoid cells in the germinal centre (G.C.) and the vast majority of lymphoid cells in the mantle-zone (M.Z.) were shown to belong to B-cell system because of the expression of ATPase and 5′N in their membranes. Some lymphoid cells positive for ANAE and B-G with a B-like pattern and for AcPh were recognizable in the G.C. In the M.Z. only a few lymphoid cells being ANAE, with a T-like pattern, and AcPh were shown to belong to the T-cell system. In contrast, in this zone a high proportion of small lymphoid cells (64%±10%) showed ANAE activity, mostly with B-like pattern. Therefore, these findings indicate that in the M.Z. a high proportion of B-cells ATPase and 5′N also display ANAE activity. By comparison of the results obtained from lymphoid tissue sections, B-CLL and immunocytoma cell suspensions and normal circulating lymphocytes we can conlude that B-ANAE-positive cells of the M.Z. do not usually appear in the peripheral blood. They circulate in large numbers only in some pathological conditions (like our reported B-CLL). Therefore, B-ANAE-positive lymphoid cells of the mantle, with a B-like staining pattern, include a wide range of subsets which exclude large lymphoid cells and plasma cells. [ABSTRACT FROM AUTHOR]