IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.

INTRODUCTION: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model. MATERIALS AND METHODS: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up. RESULTS: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules. CONCLUSIONS: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).

Expression of IMP3 in a retrospective cohort of melanomas with selective lymph node biopsy.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3), which is a member of the insulin-like growth factor mRNA-binding protein family, is expressed at high levels in many types of cancer, where it plays an important role in cell proliferation, as well as in the processes of invasion, migration, and metastasis. Its expression has also been demonstrated in malignant melanoma, but not in other benign skin lesions, which has raised the possibility of using it as a predictive and prognosis marker. Its relationship with sentinel lymph node biopsy, however, has not been explored yet. A retrospective study including 120 histological samples of patients diagnosed with malignant cutaneous melanoma in Granada, between 2012 and 2018, was developed. All patients had had a sentinel lymph node biopsy (SLNB) performed at Hospital Universitario San Cecilio. IMP3 immunostaining was simultaneously carried out in the cutaneous lesion. We observed a significant difference regarding the percentage of cells expressing IMP3 (29.73 ± 3.81 for negative SLNB vs 44.86 ± 5.91 for positive SLNB, P = .020). Our endpoint calculated according to the ROC curve of 35% was significant with P = .007. H (P = .013) and AR (P = .016) indexes, created by the percentage of positive tumor cells and the intensity of the IMP3 expression, were also statistically significant. The most optimal cut-off points to predict the positivity of the SLNB were 35 for the percentage of positive tumor cells and 70 for the H score. We found a significant association between the expression of IMP3 and the regional nodal status defined by the SLNB on malignant melanomas in our series.

Acantholytic-like malignant melanoma: an unusual morphologic variant.

We report the case of a primary cutaneous melanoma with acantholytic-like changes in a 61-year-old man. Clinical and immunohistochemic features were similar to those of other superficial spreading with vertical growth melanomas. Histologically, intraepidermal and suprabasal bullous spaces were filled by isolated tumor cells, simulating acantholytic blisters. These findings could be explained by the presence of inflammation-related extracellular fluid. Two other cases with suprabasal discohesive atypical melanocytes have recently been described. We report the first case of malignant melanoma with an intense and diffuse pattern of dyscohesion, resembling acantholysis. Recognition of this histologic pattern in malignant melanoma is important to avoid a misdiagnosis.

Clinical and histologic comparison of two different composite grafts for sinus augmentation: a pilot clinical trial.

BACKGROUND AND OBJECTIVES: Sinus augmentation is a procedure used for augmenting insufficient bone height that is often observed in the maxillary posterior areas. Many different techniques as well as bone graft regimens have been suggested for performing this procedure. It was the goal of this study to compare, clinically and histologically, two different composite grafting regimens used for sinus augmentation. MATERIAL AND METHODS: Five patients, needing a bilateral sinus augmentation to allow implant placement, were recruited for this study. Right sinuses were grafted with cortical bone (collected from overlying the sinus membrane) and bovine hydroxyapatite (HA), while the left side sinuses were grafted with overlying autologous bone plus a bioglass (BG) material. Bone core biopsies were taken at 6 months after sinus graft or at the time of implant insertion. A waiting period of 6 additional months was granted to allow healing, before prosthetic restoration and functional loading. The level of peri-implant bone was evaluated 12 months after loading. A comparative histomorphometric analysis was conducted and a statistical analysis was performed. RESULTS: All implants in both groups were functional after a 12-month loading period. No bone loss was observed radiographically or clinically in both groups. Histologic analysis revealed that both composite grafts had a high biocompatibility. In the bovine HA-containing group, minimal xenogenic graft absorption was noted. In contrast, BG group samples presented a high absorption rate with some remaining particles imbedded in new normal bone. CONCLUSIONS: Sinus augmentation using a combination of autogenous bone plus either bovine HA or BG is a predictable technique.

Validation of KDRI/KDPI for the selection of expanded criteria kidney donors. / Validación del KDRI/KPDI para la selección de donantes renales con criterios expandidos.

INTRODUCTION: KDRI / KDPI are tools use in kidney donor evaluation. It has been proposed as a substitute of, or complementary to preimplantation renal biopsy. These scores has not been validated in Spain. OBJECTIVE: 1) To investigate the concordance between KDPI and histological scores (preimplantation renal biopsy) and 2) To assess the relationship between KDRI, KDPI and histological score on graft survival in the expanded criteria donors group. METHODOLOGY: Retrospective cohort study from 1 January 1998 until 31 December 2010. RESULTS: During the study 120 donors were recruited, that resulted in 220 preimplantation renal biopsies. 144 (65%) grafts were considered suitable for kidney transplantation. 76 (34.5%) were discarded. Median follow up has been 6.4 years (sd 3.9). Median age 63.1 years (sd 8.2), males (145; 65.9%), non-diabetic (191; 86.8%) and without another cardiovascular risk factors (173; 78.6%). 153 (69.5%) donors died of cerebrovascular disease. There were significant differences in KDRI/KDPI score in both groups 1.56/89 (sd 0.22) vs 1.66/93 (sd 0.15), p<0.01). The KDPI showed moderate concordance and correlation with the histological score (AUC 0.64 / correlation coefficient 0.24, p <0.01). KDPI (HR 24.3, p<0.01) and KDRI (HR 23.3, p<0.01) scores were associated with graft survival in multivariate analysis. CONCLUSION: 1) KPDI and histological scores show moderate concordance. The utility of both scores as combined tools it has to be determined. 2) KDPI score, and especially KDRI score, are valid for estimating graft survival and combined with the biopsy can help to individualized decision making in the expanded criteria donors pool.

Sauvé-Kapandji and reverse Sauvé-Kapandji procedures for treating chronic longitudinal radioulnar dissociation with capitellum fracture.

Almost all reported cases of longitudinal radioulnar dissociation have involved fracture of the radial head, rupture of the interosseous membrane, and disruption of the distal radioulnar joint, although unusual patterns of Essex-Lopresti injury have also been described. To our knowledge, this is the first report of a chronic Essex-Lopresti variant including fracture of the capitellum. A displaced capitellum fracture must alert to the possibility of longitudinal radioulnar dissociation, even without concomitant radial head fracture or symptoms at the forearm and ulnar wrist. Successful mid-term results can be achieved by treating malunion of humeral condyle and proximal migration of the radius with simultaneous Sauvé-Kapandji procedure at the wrist and reverse Sauvé-Kapandji at the elbow.