Factors associated with local recurrence in operated osteosarcomas: A retrospective evaluation of 95 cases from a tertiary care center in a resource challenged environment.

BACKGROUND AND OBJECTIVES: Local control of disease is one of the main goals of osteosarcoma management. We conducted a retrospective evaluation of 95 operated cases of osteosarcoma over 7 years to know about the factors associated with local recurrence in resource-challenged environment of the developing world. METHODS: The factors which were evaluated and compared between local recurrence and non-local recurrence groups included demographic profile, site of tumor, whether biopsy done outside, type of surgery (limb salvage or amputation), presence of pathological fracture, vicinity of neurovascular bundle, tumor volume, histological subtype, chemotherapy induced necrosis, surgical margins, and delay in surgery. The time to local recurrence after surgery was also noted in the local recurrence group. RESULTS: At a mean follow-up of 2.8 years, biopsy done from outside the treating center and delay in surgery after completion of neo-adjuvant chemotherapy emerged as significant risk factors for local recurrence. Most of the local recurrences (80%) occurred within 12 months of the primary surgery. CONCLUSIONS: Lack of financial resources and availability of few tertiary care centers dealing with musculoskeletal oncology in the developing countries, lead to overburden with a long waiting list for tumor surgery making the scenario different from the Western world.

Developing a prognostic model for patients with localized osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate: A single-center experience of 237 patients.

BACKGROUND: Studies of baseline prognostic factors in patients with localized osteosarcoma treated without high dose methotrexate are limited. METHODS: This is single-institutional review of localized osteosarcoma patients treated without high dose methotrexate between June 2003-December 2012. A multivariate analysis of impact of baseline and treatment characteristics on outcome was performed and a prognostic model was developed based solely on baseline factors for predicting event-free survival (EFS) and overall survival (OS). RESULTS: Of 237 patients with median age of 17 years (range 2-66 yrs), neoadjuvant chemotherapy (NACT) was administered in 220 (92.82%) patients. Post NACT, 200/237 (84.38%) patients underwent surgery. At 30 months median follow-up, 5-year EFS and OS were 36.60 ± 0.03%, and 50.33 ± 0.04%, respectively. In multivariate analysis, baseline factors including duration of symptom >4 months (P < 0.001) and good performance status (PS) (P < 0.001) predicted better EFS whereas good PS (P = 0.01) and normal serum alkaline phosphatase (SAP) (P = 0.03) predicted better OS. The 5-year EFS without any risk factor (symptom duration <4 months, PS>1) was 58.7 ± 0.1%, with either one factor 31.5 ± 0.1% and with both factors 21.9 ± 0.1%. The 5-year OS without any risk factor (PS>1, elevated SAP) was 66.9 ± 0.1%, with either one factor 57.9 ± 0.1% and with both factors 25.6 ± 0.1%. CONCLUSIONS: This prognostic model assists in categorizing risk-groups within localized osteosarcoma.

Giant schwannoma of the first metatarsal: a rare entity.

Schwannomas of osseous origin are rare, and schwannomas of the short tubular bones are even rarer. These benign-looking tumors are difficult to diagnose using imaging alone. However, histopathologic evaluation of a biopsy specimen can establish the diagnosis by identifying Antoni type A and B zones. Curettage and bone grafting will probably be adequate for treatment because malignant changes are unlikely. Large lesions can require en bloc excision and reconstruction. We describe what appears to be only the second case of a schwannoma in the first metatarsal of the foot in a 48-year-old woman. The lesion was poorly contained, with obvious breaks in the cortical shell. The diagnosis was confirmed by pathologic analysis. The lesion was successfully treated with en bloc resection and reconstruction with a nonvascularized fibular graft.

Epithelioid hemangioma of distal femoral epiphysis in a patient with congenital talipes equinovarus.

BACKGROUND: Epithelioid hemangioma (EH) is a rare benign vascular lesion of soft tissue and bone, characterized by endothelial cells with epithelioid or histiocytoid appearance. Though tubular bones, flat bones, vertebra and short bones are common sites for this lesion, the epiphyseal involvement is extremely rare. We present an unusual case of EH of the distal femur in a young boy. CASE REPORT: A 12-year-old boy who had congenital talipes equinovarus of the right foot presented with progressively increasing pain in the right lower thigh for six months. Physical examination revealed muscular atrophy of the right lower limb and a moderately tender swelling in the medial aspect of the right knee without restriction of knee movement. An X-ray revealed an osteolytic lesion, which appeared iso- and hypointense on T1W and hyperintense on T2W MRI images in the distal epiphysis and adjacent metaphysis of the right femur. A radiological diagnosis of chondroblastoma was entertained. The patient was treated with curettage and bone grafting. Histopathology showed a tumor composed of thin-walled arteriolar capillaries lined by large, polyhedral epithelioid endothelial cells with vesicular nuclei, finely distributed nuclear chromatin, and moderate amount of eosinophilic cytoplasm. The endothelial cells were strongly immunopositive for CD34. Mitotic activity was low and the Ki-67 proliferative rate was <2%. A diagnosis of EH was made. EH is a benign lesion and it should be differentiated from its histologically similar malignant counterparts such as epithelioid hemangioendothelioma and epithelioid angiosarcoma as the lesion can be successfully treated with curettage or resection.

High burden of metastases and poor outcome in pelvic PNET.

Data on prognostic factors in pelvic PNET are minimal. We analyzed patients with pelvic PNET treated between June 2003 and November 2011 for prognostic factors. Forty-eight (13%) of 374 patients with PNET were pelvic PNET with median age 14.5 years (range: 5-33); 31 (65%) had metastases. After median follow-up of 20.4 months (range: 1.3-64.9), 3-year EFS, OS, and local-control-rate were 13.5 ± 5.5%, 15.4 ± 9%, and 41.3 ± 14.9%, respectively. Hypoalbuminemia (≤3.4 g/dl) predicted inferior EFS and OS for both entire cohort and metastatic group. All patients with hypoalbuminemia (n = 10) had low BMI as compared to 23/38 without hypoalbuminemia (P = 0.02).

Role of locking plates in treatment of difficult ununited fractures: a clinical study.

OBJECTIVE: To present our experience in treatment of difficult ununited long bone fractures with locking plate. METHODS: Retrospective evaluation of locking plate fixation in 10 difficult nonunions of long bone fractures was done. Fixation was done with locking plate for femoral shaft fracture (3 patients), supracondylar fracture of femur (gap nonunion), fracture of clavicle, fracture of both forearm bones (radius and ulna) fracture of ulna, fracture of shaft of humerus, fracture of tibial diaphysis and supracondylar fracture of humerus (one patient each). Five fractures had more than one previous failed internal fixation. One patient had infected nonunion which was managed by debridement with cast immobilization followed by fixation with locking plate at six weeks. Seven fractures were atrophic, two were oligotrophic, and one was hypertrophic. Fibular autograft was used in 2 cases and iliac crest cancellous bone graft used in all the patients. RESULTS: Minimum follow-up was 6 months (range, 6 months to 2.5 years). Average time for union was 3.4 months (range 2.5 to 6 months). None of the patients had plate-related complications or postoperative wound infections. CONCLUSION: Along with achieving stability with locking compression plate, meticulous soft tissue dissection, acceptable reduction, good fixation technique and bone grafting can help achieve union in difficult nonunion cases. Though locking plate does not by itself ensure bony union, we have found it to be another useful addition to our armamentarium for treating difficult fracture nonunions.

Role of vascular endothelial growth factor as a tumour marker in osteosarcoma: a prospective study.

PURPOSE: A prospective study was undertaken to evaluate the diagnostic and prognostic significance of serum levels of vascular endothelial growth factor (VEGF) in patients with primary localised osteosarcoma. METHODS: Serum VEGF levels were measured by an enzyme-linked immunosorbent assay (ELISA) in blood samples collected prechemotherapy, postchemotherapy, and postsurgery in 40 patients with histologically proven primary osteosarcoma. Comparison was made between serum VEGF level of healthy controls (n = 10) and prechemotherapy patient sera to evaluate its diagnostic potential. Serum VEGF levels of patients with and without metastasis were compared. Immunohistochemical staining was done to establish the correlation between serum and tissue VEGF expression. The Kaplan-Meier curve was used for survival analysis RESULTS: No significant relationship was observed between serum VEGF levels and age, gender, tumour size, local recurrence or histopathological subtypes of osteosarcoma. We observed significantly raised mean serum VEGF in patient sera compared with healthy controls (p = 0.001). Significant fall in mean serum VEGF level was observed following chemotherapy (p = 0.001). Patients who developed metastases had significantly higher serum VEGF levels compared with the nonmetastatic group (P = 0.001). Serum VEGF levels correlated well with VEGF expression in tissues. CONCLUSION: Serum VEGF levels might prove to be of diagnostic, predictive and prognostic value in patients with primary osteosarcoma, although further studies with larger sample size and longer follow-up is needed to support the hypothesis.

Expression of vascular endothelial growth factor in Ewing's sarcoma.

PURPOSE: Vascular endothelial growth factor (VEGF) is the most potent stimulator of angiogenesis. The aim of this study was to evaluate the role of serum VEGF as a diagnostic, predictive and prognostic marker in Ewing's sarcoma. METHODS: Patients with histopathologically proven diagnosis of Ewing's sarcoma without prior chemotherapy or radiotherapy were invited to take part in the study. Pre-chemotherapy, post-chemotherapy and post-surgery blood samples were collected for analysis of serum VEGF levels. Blood samples from ten sex- and age-matched healthy volunteers were collected for estimation of VEGF levels to act as control. Human VEGF Elisa kit (Bender Medsystem, Austria) was used to assess the serum VEGF levels. RESULTS: A total of nine cases of Ewing's sarcoma were included in the study. Mean age in the group was 12.44 years (range, seven to 18 years). Mean and median serums VEGF level in the study population were 4,547.78 pg/ml and 3,780.00 pg/ml, respectively. Ten age- and sex-matched healthy volunteers were selected as controls. No significant correlation was obtained between serum VEGF, age, sex and tumour size. Mean serum VEGF was significantly raised in the study group as compared to controls (p = 0.001). We observed a significant decline in serum VEGF level following neoadjuvant chemotherapy (p = 0.008). No correlation could be established between serum VEGF level pulmonary metastasis and overall survival. CONCLUSION: Serum VEGF might have a role as a diagnostic and predictive marker in patients with Ewing's sarcoma.

Prediction of chemotherapy response by PET-CT in osteosarcoma: correlation with histologic necrosis.

BACKGROUND: The current standard for neoadjuvant chemotherapy (NACT) response evaluation in osteosarcoma is histopathologic necrosis (HN). However, it is accessible only after NACT completion and may get affected by confounding factors. Thus, noninvasive surrogate such as (18)Fluorine-Fluorodeoxyglucose-positron emission tomography-computerized tomography (PET-CT) scan would be useful to individualize therapy. METHODS: Thirty-one treatment naive osteosarcoma patients evaluated prospectively by PET-CT scan preceding and after 3 cycles of NACT and surgery during 2006 to 2008. Various anatomic and metabolic parameters of PET-CT scan were compared with HN (good response ≥90% HN) as reference standard. Receiver operating characteristic curves were generated to assess the best threshold and predictability. RESULTS: Median age was 17 years; 25 were male patients and 23 were nonmetastatic. Ten cases were good, whereas 21 cases were poor histologic responders. PET-CT parameters including post-NACT (2) and pre-NACT (1) standard uptake value (SUV)max ratio (SUV2:SUV1), SUV2, pre-NACT and post-NACT volumes (V1and V2), change in V after NACT, pre-NACT and post-NACT metabolic burden (MB) and change in MB after NACT correlated with HN. Two independent predictors were identified in stepwise multivariable analysis; if V1 ≤300 mL and SUV2:SUV1 ≤0.48, observed good histologic response proportions was 83%, whereas if V1 >300 mL and SUV2:SUV1 >0.48, it was 0%. CONCLUSIONS: NACT response can be predicted reliably by PET-CT scan early in disease course (even at baseline) and PET-CT parameters correlate well with HN. MB seems to be sensitive substitute for response evaluation. Independent predictors may have wider clinical applications if further validation can be done.

Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis.

BACKGROUND: Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. OBJECTIVE: To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. MATERIALS AND METHODS: Thirty-one treatment-naïve osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. RESULTS: Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. CONCLUSION: In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma.

A single incision surgical new anterior technique for forequarter amputation.

BACKGROUND: Conventionally described standard techniques of forequarter amputation may not be suitable for patients presenting with neglected or maltreated very large tumors of the proximal humerus. PATIENTS AND METHODS: Eleven patients with unsalvageable malignant tumors of proximal humerus, who underwent forequarter amputation using a new technique between Jan 2008 to March 2010, were retrospectively analysed. This new single incision anterior approach involves supine positioning of patients, ligation of axillary vessels in the axilla followed by resection of muscles from lateral border and inferior angle of scapula, resection of lateral one-third of clavicle; resection of muscles from vertebral border and superior angle of scapula by applying superolateral traction without any incision over acromioclavicular axis or posterior scapular skin. RESULTS: The average age was 16.27 year and minimum follow-up was 6 months (range 6-24 months). There were seven males and four females. Average duration of surgery was 62 min (range 55-90). Blood loss ranged from 400 to 750 ml. One patient had superficial infection and one patient with metastatic lesion died at 6 months follow-up. CONCLUSIONS: This technique is safe, easy, less time consuming, involves small single incision in supine position, has better wound healing and can be used for both small and large tumors of proximal humerus with or without involvement of axillary vessels. Although there was no local recurrence for last 24 months but a long term follow-up is required to comment on its actual rate.

Femoral prosthesis neck fracture following total hip arthroplasty: a case report.

Fracture of the femoral prosthesis neck following total hip arthroplasty is not common. We report a case of femoral prosthesis neck fracture in an adult male patient following modular, uncemented total hip arthroplasty. This case report further emphasizes the importance of the potentially high loading situation in the prosthetic femoral neck. On the other hand, the occurrence of a femoral prosthesis neck fracture in a cementless system denotes a well fixed distal stem and calls for a difficult revision procedure usually requiring an extended trochanteric osteotomy for stem retrieval.

Massive recurrent tumoral calcinosis: a rare presentation.

Tumoral calcinosis is an autosomal recessive, metabolic disorder, characterised by deposition of calcium salts in the subcutaneous tissues of the body. We present a case of massive, recurrent tumoral calcinosis in a 32-year-old male patient.

Morphometric variations of the lateral surface of calcaneus: Can standard plate sizes fit all?

PURPOSE: Displaced intraarticular fractures of the calcaneum often require plate fixation. The complex fractures are usually fixed with standard lateral plates and are approached via the extensile lateral approach which is fraught with the risk of wound complications. Oversized calcaneal plates produce tension on the wound closure site and can, thus result in wound healing problems. The current study analyses the morphometry of the lateral surface of the calcaneus for the ideal configuration of the calcaneal plates for Indian patients using a CT based analysis of intact calcanei. METHODS: Fifty CT based studies of normal calcanei were retrospectively analyzed using Horos® software version 3.3.5. The cross-section of the lateral third of calcaneum was assessed for the morphometric measurements relevant to the dimensions of the standard plating devices for calcaneum. We measured the overall plating length of calcaneum, the vertical heights at the anterior process and calcaneal tuberosity, the height of the posterior facet, the lengths of the anterior process, and the posterior facet. The inclination angles of the posterior facet, cuboid facet were also measured. The findings were compared between male and female cases. RESULTS: The mean plating length of the calcaneus was 60.06 ± 4.05 mm. The mean vertical height of the anterior process and the calcaneal tuberosity were 24.3 ± 2.71 mm and 39.48 ± 4.73, respectively. The length of the anterior process and the posterior facet were 21.36 ± 1.72 and 25.02 ± 4.17, respectively. The mean Gissane angle and the angle of inclination of posterior facet in relation to the plating length were 118.04 ± 5.99° and 47.3 ± 5.20°. The mean anterior slant angle of the cuboid facet was 96.64 ± 4.39°. Significant differences were observed in the measurements among male and female groups except for the angular parameters. CONCLUSION: The current analysis suggests the individual morphometric variations of the lateral plating surface of the calcaneus. Although female calcanei have smaller dimensions compared to male calcanei, the angular parameters are comparable among the two groups. Considering the wide variations in the majority of the morphometric parameters, it is difficult to standardize the plate dimensions. However, a few serial increments in the plate dimensions can help in providing the best fit rather than an ideal fit. Also, the plates should be available with multiple inclination angles of the facet limbs according to the local population variations.

Noninvasive imaging surrogate of angiogenesis in osteosarcoma.

PURPOSE: Measurement of tumor angiogenesis by qualitative analysis of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI), and its association with diffusion-weighted (DW)-MRI and glucose metabolism using positron emission tomography-computerized tomography (PET-CT) scan has not been explored in osteosarcoma. Present study was aimed to evaluate the potential of these surrogates. PATIENTS AND METHODS: Thirty-one treatment naive patients with osteosarcoma underwent MRI and PET-CT preceding and following three cycles of neoadjuvant chemotherapy (NACT) and surgery. Time intensity curves (TICs) representing low microvascular permeability is persistent type while that of high permeability are plateau and washout types. Vascular endothelial growth factor (VEGF) expression was assessed in biopsy and resected specimens by immunohistochemistry. The sample was considered VEGF positive when intensive positive staining of VEGF was observed in >10% of the tumor cells in biopsy or resection specimens. RESULTS: TIC could correctly identify all 28 VEGF positive samples at baseline and 24/25 (96%) of VEGF positive samples and 5/6 (83%) of VEGF negative samples after NACT. The change in curve pattern from washout/plateau to persistent type was in agreement with corresponding decrease in microvascular permeability, that is, VEGF expression. For persistent type of TIC, mean change in VEGF was 73.3 +/- 43.2% and for plateau and washout type of TIC it was 19.54 +/- 45% and 16.66 +/- 28.86%, respectively (P

Is sclerotherapy better than intralesional excision for treating aneurysmal bone cysts?

BACKGROUND: Minimally invasive approaches such as sclerotherapy have been introduced to treat aneurysmal bone cysts. Sclerotherapy has been associated with reasonable healing rates during the past two decades. However, it is unclear whether sclerotherapy compares with the more traditional extended curettage and bone grafting. QUESTIONS/PURPOSES: We therefore compared the healing rates and functional scores in patients having percutaneous repetitive sclerotherapy using polidocanol (Group 1) with those with intralesional excision (extended curettage with a high-speed burr) and bone grafting (Group 2) for treatment of aneurysmal bone cyst. PATIENTS AND METHODS: We randomly divided 94 patients into two treatment groups. We assessed healing rates (primary outcome measure), pain relief, time to healing and recurrence, hospital stay, and the Enneking functional score. Forty-five patients from Group 1 and 46 from Group 2 were available for study. The minimum followup was 3.2 years (mean, 4.4 years; range, 3.2-6.1 years). RESULTS: At last followup, 93.3% in Group 1 and 84.8% in Group 2 had achieved healing. Complications in Group 1 were minor and resolved. In Group 2, three patients had deep infections and five had superficial infections, and two had growth disturbances. Although the healing rates were similar, we found higher rates of clinically important complications, worse functional outcomes, and higher hospital burden associated with intralesional excision. CONCLUSIONS: Repetitive sclerotherapy using polidocanol is a minimally invasive, safer method of treatment for aneurysmal bone cysts compared with intralesional excision and bone grafting. In this preliminary study, we found similar recurrence rates for the two treatment methods, however, this will require confirmation in larger studies. LEVEL OF EVIDENCE: Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Total hip arthroplasty in patients with active tuberculosis of the hip with advanced arthritis.

UNLABELLED: Osteoarticular tuberculosis (TB) in the hip and other joints is increasing and patients in developing countries commonly present with advanced joint destruction. We asked whether TB is reactivated after THA in these patients. We retrospectively reviewed 12 patients with an average age of 45 years who had advanced stages of hip destruction secondary to mycobacterium TB and who were treated with primary THA and prescribed perioperative antituberculous medication for 12 to 18 months postoperatively. Diagnosis in all these patients was confirmed by histopathology and culture. The minimum followup was 25 months (average, 41 months; range, 25-58 months). We observed no reactivation of TB in 11 patients who had Harris hip scores ranging from 86 to 97. One patient who postoperatively did not comply with the antituberculous chemotherapy had reactivation and superimposed infection through a nonhealing sinus tract; that patient underwent component removal and resection arthroplasty. When the infected tissue can be débrided and adequate antituberculous therapy is instituted the outcome of joint arthroplasty may not be adversely affected. THA in the tuberculous hip has a low risk of reactivation and produces good functional results. LEVEL OF EVIDENCE: Level IV, therapeutic case series (no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Do locking plates have a role in orthopaedic oncological reconstruction.

BACKGROUND: Role of locking plate in skeletal reconstruction after resection of bone tumours in Indian patients. MATERIALS AND METHODS: Retrospective evaluation of skeletal reconstruction using locking plate in 20 cases of long bone tumours was done. Reconstruction was done in 12 patients following limb salvage surgery, internal fixation of pathological fracture in seven bone tumours and one angiomatous tumour. There were 12 females and 8 male patients. RESULTS: Average age at the time of surgery was 30.1 years (range 10-58). Minimum follow-up was 11 months (range 11-38). Average time for union in pathological fractures was 4 weeks and 120 days after limb salvage surgery. Vicryl mesh was used to contain the morcellized allograft and cancellous iliac crest in 17 cases. Eighteen reconstructions were intact at an average follow-up of 17 months. Two failed reconstructions included one plate breakage and one screw pull out. CONCLUSION: Use of locking plate does not ensure the bony union at the site of reconstruction but it expedite it and allow early mobilization of joints and weight bearing particularly in Indian patients with late presentations. Careful selection of patients and proper preoperative planning including length of resection are essential for optimal outcomes and to minimize complications. Reconstruction should be supported by cortico-cancellous autograft/allograft for stabilization and union at junction of host and autograft/allograft bone and should be given adequate protection. Vicryl mesh helps in containing the morcellized grafts along the long axis of reconstruction.

VEGF expression as a prognostic marker in osteosarcoma.

BACKGROUND: The vascular endothelial growth factor (VEGF) pathway is the key regulator of angiogenesis. In osteosarcoma baseline VEGF is of proven prognostic value but prognostic potential of post-NACT VEGF expression is largely unexplored. PROCEDURE: Treatment naive patients with osteosarcoma were subjected to initial staging workup followed by three cycles of neoadjuvant chemotherapy (NACT) and surgery; resected tumors were assessed for histological necrosis by Huvos grading. Initial biopsy and resected tumor specimens post-NACT were examined for VEGF expression by immunohistochemistry. Positive VEGF expression was considered when intensive positive staining was observed in >10% of the tumor cells. VEGF expression at baseline was compared with grade of tumor; pre-NACT and post-NACT VEGF expression were compared with histological necrosis. Receiver operating characteristic curves were generated to assess best threshold and predictability. RESULTS: A total of 31 patients were recruited with median age of 17 years (range 5-66 years); male/female ratio was 25:6; 23 patients (74%) were non-metastatic. At baseline, there was 90% concordance between positive VEGF expression and higher histological grade (28/31); baseline VEGF expression did not correlate well with stage and histological necrosis. Twenty-one (67%) were poor and 10 (33%) were good histologic responders; post-NACT VEGF expression as well as VEGF change following NACT significantly correlated with histological necrosis. CONCLUSION: Positive VEGF expression in surviving tumor cells post-NACT in resected tumors appears to be an important negative prognostic factor in osteosarcoma which may help future therapies to be identified according to the angiogenic potential of the disease.

Her-2/neu, p-53, and their coexpression in osteosarcoma.

BACKGROUND: There is controversy regarding the patterns and prognostic significance of Her-2/neu and p-53 expression in osteosarcoma. Further, their combined expression has not been studied. PROCEDURE: Prechemotherapy biopsy specimens of 63 osteosarcoma patients from June 2004 to August 2006 were analyzed for Her-2/neu and p-53 using immunohistochemistry and compared with grade, stage, and morphologic subtype of tumor. RESULTS: There were 59 high-grade tumors; 32 of 63 had metastases. Histopathologic types included 36 of 63 osteoblastic and 18 of 63 chondroblastic subtypes. Male sex (P=0.045) and chondroblastic type (P=0.004) were associated with metastatic disease. Her-2/neu cytoplasmic staining was seen in 30 of 63 (47.1%) cases, 4 of 30 had additional membranous staining, 17 of 30 were metastatic, and 29 of 30 were high-grade tumors. Staining grade was 3+ in 10 of 30 samples whereas staining intensity 3+ was observed in 26 of 30 samples. Her-2/neu 3+ staining grade was significantly associated with chondroblastic subtype (6/18, P=0.026). P-53 staining was seen in 20 of 63 (31.74%) cases (all high grade), of which 11 were metastatic. Staining grades 3+ and 4+ were seen in 16 of 20 samples whereas staining intensity 3+ in 13 of 20 samples. P-53 expression was higher in chondroblastic (7/18, P value was not significant) and fibroblastic (3/3, P<0.05) subtypes. Coexpression of Her-2/neu and p-53 was seen in 10 cases (15.87%); 3 of 10 cases showed Her-2/neu membranous staining (P=0.01). CONCLUSIONS: Her-2/neu (47.1%), p-53 (31.74%), and their combined expression (15.87%) were not related to grade or stage of tumor. Chondroblastic subtype was associated with staining grade 3+ of Her-2/neu staining whereas coexpression of Her-2/neu and p-53 was significantly associated with membranous Her-2/neu staining.