P Robbins

University of Western Australia, Perth City, Western Australia, Australia

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Publications (13)32.84 Total impact

  • M H Zheng · P Robbins · J Xu · L Huang · D J Wood · J M Papadimitriou ·
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    ABSTRACT: Giant cell tumour of bone (GCT) is a benign primary neoplasm of a bone characterised by distinctive clinical, radiological and pathological features. Females are slightly more often affected than males, and the majority of patients present between the ages of 20 and 50. GCT is locally aggressive and produces expansive and lytic lesions, most commonly in the epiphyses of long tubular bones. Histologically, it is composed of oval and spindle mononuclear cells, uniformly distributed amongst which are large multinucleated osteoclast-like giant cells. Although the term "Giant Cell Tumour" (and the erroneous historical term 'osteoclastoma') may imply that it is the multinucleated giant cells which are responsible for the proliferative capacity of the tumour, there is evidence that the stromal-like cells, the major component of the mononuclear cell population, represent the true neoplastic component of the neoplasm. The diagnosis and management of conventional GCT are often challenging and there is considerable current interest in its pathobiology. The precise histogenesis of GCT and the nature of its varying cellular constituents have remained a matter of some controversy. Factors influencing the clinical course and biological aggression of GCT are also unclear. In this selective review, the clinicopathological characteristics of GCT are summarised and current areas of interest in the study of the neoplasm are presented and discussed. Lastly, a hypothetical model of the mechanism of histogenesis and the biological behaviour of GCT is presented.
    Histology and histopathology 02/2001; 16(1):297-307. · 2.10 Impact Factor
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    ABSTRACT: The production of vascular endothelial growth factors (VEGF), a major cause of neoangiogenesis, is a prerequisite for tumor growth and invasion. VEGF have also been shown to be important for the formation of osteoclasts. Because giant cell tumors of bone (GCT) are frequently hypervascular and have the ability to recruit macrophages and multinucleated osteoclast-like giant cells, we evaluated the levels of VEGF gene transcript in several of these tumors using Northern blot analyses, semiquantitative reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry. Our results showed that three major isoforms of VEGF (121, 165, and 189) were expressed in all cases of GCT investigated, with isoform 121 transcripts the most abundant. By both FISH and immunohistochemistry, we have shown that VEGF was present in spindle-shaped stromal-like tumor cells, round macrophage-like cells, and osteoclast-like multinucleate giant cells. Moreover, we have shown that the levels of VEGF gene expression but not microvessel density correlated with Enneking's clinical stage of GCT. There were higher levels of VEGF gene expression in stage III GCT than in stage I/II GCT (P < .0357). In conclusion, our results indicate that overexpression of VEGF may be associated with the advanced stage of the neoplasm.
    Human Pathlogy 07/2000; 31(7):804-12. DOI:10.1053/hupa.2000.8441 · 2.77 Impact Factor
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    ABSTRACT: The correlation between angiogenesis as assessed by endothelial cell proliferation in blood/lymphatic vessels in primary breast carcinomas, and axillary lymph-node metastasis was studied using a case-control design. Primary breast carcinomas, < 2 cm in diameter, from 26 axillary node positive patients (case), were compared with neoplasms from 45 node-negative patients (control). Vascularity, as assessed by vessel density, and endothelial cell proliferation were measured in a single tissue section using a double immunohistochemical staining technique using MIBI (Ki-67) and FVIII antibodies. No association between vascularity and node status was found (P > 0.70). Node positive breast carcinomas had, on average, significantly smaller proliferating vessels (140+/-7 microm in perimeter) in the primary lesion when compared with node negative tumours (164+/-7 microm in perimeter (P < 0.02). In addition, the frequency of relatively small vessels (less than 180 microm in perimeter) with proliferating endothelium was higher in node positive carcinomas than lymph-node negative neoplasms (P < 0.03). This association between node status and the size and frequency of blood/lymphatic vessels with proliferating endothelium in primary carcinoma may have important implications in metastasis.
    The Breast 02/2000; 9(1):28-34. DOI:10.1054/brst.1999.0082 · 2.38 Impact Factor
  • H Elsaleh · D Joseph · M Levitt · A House · P Robbins ·
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    ABSTRACT: The aim of the present study was to investigate the effectiveness and toxicity of pre-operative chemoradiation in locally advanced rectal cancer (T3-T4). Forty-seven patients were assessed (38 T3 and nine T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy in 25 fractions over 5 weeks. Bolus 5-fluorouracil (5-FU) was delivered 500 mg/m2 on days 1, 2, 3 and days 22, 23, 24. Total mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. All patients undergoing chemoradiation completed therapy as planned, with no treatment-related interruptions. The regimen had a low acute toxicity profile with an estimated 50% or greater response in 38 out of 47 patients (four patients had complete responses). Forty-three (97%) of 44 patients who underwent surgery were operable. Patients who were operated on between 4 and 7 weeks had a statistically better response then those who were operated on after 7 weeks (P = 0.013; Fisher's exact test). Eight of 10 patients who were considered to be inoperable prior to the treatment underwent total mesorectal excision with negative radial margins. Anastomotic leakage occurred in four patients (9%); one required surgical intervention. Wound infection occurred in three patients (6%); one patient required re-exploration for haemorrhage. Delayed complications occurred in three patients (6%); one requiring surgery for a stomal stricture. After a median follow-up of 20 months, two patients (4%) had developed local recurrence. The pre-operative chemoradiation regimen employed had a low acute toxicity profile and all patients completed therapy. The majority of patients considered inoperable prior to receiving this treatment underwent successful excision. Appropriately fractionated pre-operative chemoradiotherapy is a reasonable option in this disease and deserves further evaluation.
    Australian and New Zealand Journal of Surgery 11/1999; 69(10):737-42. DOI:10.1046/j.1440-1622.1999.01677.x
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    ABSTRACT: The purpose of the present paper was to update a prospective analysis (H Elsaleh et al. unpubl. data, 1997) investigating the effectiveness and toxicity of pre-operative pelvic radiotherapy with modest dose 5-fluorouracil (5-FU) in locally advanced rectal cancer (T3-T4). A total of 31 patients were assessed (28 T3 and three T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy to the International Commission on Radiation Units and Measurements (ICRU) point in 25 fractions over 5 weeks. A radiosensitizing dose of 5-FU was delivered at 500 mg/m2 on days 1, 2 and 3, and days 22, 23 and 24. Mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. Patients had a low toxicity profile; an estimated 50% or greater response was seen in 24 out of 31 (two complete responses). There were no surgical difficulties achieving resection. No late complications were documented, although follow-up was short. In locally advanced rectal cancer, pre-operative chemo-radiotherapy had a low toxicity profile. Appropriately fractionated pre-operative chemo-radiotherapy is a reasonable option in this disease and should be further evaluated. The optimal method of delivery of the radiosensitizing agent (5-FU) is the subject of further investigation.
    Australasian Radiology 06/1999; 43(2):215-9. DOI:10.1046/j.1440-1673.1999.00653.x · 0.51 Impact Factor
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    R Soong · F Grieu · P Robbins · B Dix · D Chen · R Parsons · A House · B Iacopetta ·
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    ABSTRACT: Alterations of the p53 gene and the p53 protein are common in a wide spectrum of human malignancies. In several tumor types, p53 gene mutation and/or p53 protein overexpression correlate with a more clinically aggressive phenotype as judged by worse patient survival. This has not been clearly demonstrated to be the case in colorectal cancer. Herein, we report results of the prognostic significance of p53 protein accumulation and gene mutation in a large series of colorectal cancers (n = 541) with long patient follow-up (mean, 87 months). The large majority of patients (95%) received no postoperative systemic adjuvant therapy. The incidence of p53 accumulation detected by immunohistochemistry with the monoclonal antibody DO-7 was 30%, whereas the incidence of p53 gene mutation in exons 5-8 detected using PCR-single strand conformation polymorphism was 36%. Accumulation of p53 protein was associated with improved patient survival independent of tumor stage or grade (hazard ratio, 0.66; 95% confidence interval, 0.47-0.93; P = 0.017). A marked difference was observed depending on the location of the tumor: tumors originating in the distal colon showed a strong association between the presence of p53 accumulation and improved patient survival (P = 0.003), but this was not the case for those located in the proximal colon. Dukes' stage C tumors, but not stage B, also showed an association between p53 accumulation and better outcome (P = 0.013). Mutation of the p53 gene was associated with a trend toward improved survival, particularly in the distal tumors. Our results demonstrate that in some tumor types, the presence of p53 abnormalities can correlate with better prognosis.
    Clinical Cancer Research 09/1997; 3(8):1405-11. · 8.72 Impact Factor
  • R Bell · G Makin · P Robbins · T Robertson · A K House ·
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    ABSTRACT: The effects of hypothermic injury to the liver were investigated on an isolated perfusion circuit by comparing porcine livers with varying degrees of preservation injury. A group of unstored livers (n = 5) were compared to livers stored in University of Wisconsin (UW) solution for 18 h (n = 5), and a group of livers stored in Hartmann's solution for 18 h (n = 5). We observed that the degree of platelet sequestration was directly related to the severity of the preservation injury. After 2 h of isolated liver perfusion, the perfusate platelet count fell from 148 +/- 14 x 10(9)/L to 84 +/- 13 x 10(9)/L for control livers. In comparison for livers stored in UW solution, the platelet count fell from 173 +/- 43 x 10(9)/L to 61 +/- 14 x 10(9)/L representing a 64.8% fall, while for those stored in Hartmann's solution, an even more profound fall from 152 +/- 36 x 10(9)/L to 19 +/- 9 x 10(9)/L (87.5% fall) was observed. The difference between the UW-stored and Hartmann's-stored livers was significant (P < 0.05). However, using this model, the degree of leukocyte sequestration did not differentiate the groups. Both histological and ultrastructural examination of liver biopsies taken immediately following revascularization demonstrated that for mild degrees of preservation injury following hypothermic storage, changes occur to the sinusoidal lining cells well before changes to the parenchymal elements. These findings substantiate the hypothesis that the primary injury associated with hypothermia involves the sinusoidal lining cells (non-parenchymal elements), that it is predominantly a reperfusion phenomenon and that efforts at improving preservation should therefore be targeted primarily at these cells and not the hepatocytes.
    Australian and New Zealand Journal of Surgery 07/1997; 67(7):442-7.
  • G.F Sterrett · J Harvey · P Robbins · N de Klerk ·

    Human pathology 06/1996; 27(6):618. DOI:10.1016/S0046-8177(96)90174-4 · 2.77 Impact Factor
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    ABSTRACT: Although giant cell tumor of bone (GCT) is generally considered to be an uncommon benign neoplasm, it can pursue an aggressive course with local recurrence and metastasis. Attempts to predict the biological behavior of GCT with histopathological parameters, however, have not been successful. The urokinase-type plasminogen activation system has been implicated in tumor invasion and metastasis and abnormalities of the components of this system have been found in several malignancies. In this study we postulated that the urokinase-type plasminogen activation system associated with bone destruction and local invasion is present in GCT. We therefore evaluated the mRNA levels for urokinase-type plasminogen activator (u-PA), urokinase-type plasminogen activator receptor (u-PAR), and plasminogen activator inhibitor type 1 (PAI-1) by using Northern blot analysis and in situ hybridization in four cases of GCT and spindle-shaped mononuclear cells at the 35th passage from a GCT. Our results showed that giant cell tumors of bone contained variable levels of u-PA, u-PAR, and PAI-1 mRNA, respectively, 2.3, 1.4, and 3.2 kb in size. In situ hybridization showed that u-PA, u-PAR, and PAI-1 mRNA were expressed in both the mononuclear cells and the osteoclast-like giant cells; the signal for u-PA mRNA in the spindle-shaped mononuclear cells was more intense than that in the osteoclast-like multinuclear giant cells. Some spherical mononuclear cells (macrophage-like cells) expressed high levels of PAI-1 mRNA in comparison with the spindle-shaped mononuclear cells. In addition, the 35th passaged spindle-shaped mononuclear cells were used to study the gene expression of u-PA during cell proliferation. The results showed that the level of u-PA mRNA increases after adding 10% fetal calf serum to quiescent cells. The induction was maximal at 16 hours and remained high during 48 hours of treatment. In conclusion, even though osteoclast-like cells are ultimately responsible for the bone resorption of GCT, the mononuclear neoplastic cells of GCT may also be involved in degradation of the extracellular matrix during invasive growth by facilitating the urokinase plasminogen activation system. In addition, our observation of upregulation of u-PA mRNA in spindle-shaped mononuclear cells after serum stimulation indicated that u-PA production may be linked to tumor growth.
    American Journal Of Pathology 01/1996; 147(6):1559-66. · 4.59 Impact Factor
  • P Robbins · S Pinder · N de Klerk · H Dawkins · J Harvey · Sterrett GF · I Ellis · C Elston ·
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    ABSTRACT: Interobserver variation in the histological grading of breast carcinoma was investigated using the hypothesis that optimal fixation, more precise grading guidelines, some experience, the use of training and test sets, and a comparison of results with an expert group might allow higher levels of agreement. For the training sets sections from 50 consecutive cases of breast carcinoma received at the Sir Charles Gairdner Hospital (SCGH) and fixed in both B5 and buffered formal saline (BFS) were graded by consensus of three pathologists at the SCGH and independently by consensus of two pathologists at the Nottingham City Hospital (NCH) using a modified Scarff-Bloom-Richardson histological grading system with guidelines as suggested by NCH pathologists. The section quality and degree of preservation of nuclear morphology were judged by NCH pathologists to be superior for B5-fixed material. Complete agreement in grade between SCGH and NCH results was achieved for 83.3% of B5-fixed cases and 73.5% of BFS-fixed cases (P = .05) with relative disagreement rates (RDRs) of 0.15 and 0.29 and kappa statistic values of 0.73 and 0.58, respectively. Approximately 80% complete agreement was achieved for tubule formation, nuclear score, and mitotic count, with RDRs ranging from 0.19 to 0.27 and kappa values from 0.46 to 0.69. There was a consistent bias in the SCGH results toward a higher tubule score in both B5- and BFS-fixed material because of a difference in interpretation of cribriform or complex gland patterns and a consistent bias in SCGH results toward a lower nuclear size/pleomorphism score for B5 and BFS material. For the test set sections from 50 further consecutive cases of breast cancer fixed in B5 were examined using similar criteria but taking into account the sources of error shown by the training set. Approximately 80% complete agreement was again achieved for grade components and grade (RDRs, 0.18 and 0.72). Systematic bias was reduced in the test set, but no other improvement was observed. Of the tumors designated as grade I by NCH, 87.5% were called grade I tumors by SCGH in the B5 training set, 84.6% in the B5 test set, and 66.6% in the BFS training set. The levels of agreement shown in both the training and test sets were satisfactory and represented a significant improvement over our previous study, suggesting that experience and precise grading guidelines are of value. The similar levels of agreement in training and test sets suggest that reasonable results can be achieved without direct training by expert groups.(ABSTRACT TRUNCATED AT 400 WORDS)
    Human Pathlogy 09/1995; 26(8):873-9. DOI:10.1016/0046-8177(95)90010-1 · 2.77 Impact Factor
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    B Dix · P Robbins · S Carrello · A House · B Iacopetta ·
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    ABSTRACT: Immunocytochemistry (ICC) has been used routinely to stain for p53 overexpression in a range of human tumours. The underlying assumption has been that positive staining indicates a mutation in the p53 coding sequence. Recently, however, discordancy has been observed and the accuracy of ICC as a marker of p53 gene mutation has been questioned. In this study of 109 colorectal adenocarcinomas, we compared ICC staining with p53 gene mutations detected by single-strand conformation polymorphism (SSCP) analysis. Concordancy between the two techniques was found in 69% of tumours. ICC-positive/SSCP-negative cases accounted for 20% of tumours and ICC-negative/SSCP-positive cases for the remaining 11%. These results caution against the assumption that p53 protein overexpression is always associated with a gene mutation. Epigenetic phenomena may account for a significant proportion of ICC-positive tumours. Images Figure 1 Figure 2 Figure 3
    British Journal of Cancer 11/1994; 70(4):585-90. DOI:10.1038/bjc.1994.355 · 4.84 Impact Factor
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    ABSTRACT: Describes an artificial neural network (ANN) architecture for constructing maximum entropy (MaxEnt) models based on discrete distributions. Entropy is maximized by a partition function method involving the use of Lagrange multipliers which is capable of implementation by an ANN architecture. The maximum entropy network (MaxEN), consists of a training module and a testing module of interconnected processing elements. The practical use of the MaxEN network is illustrated with an application in the clinical management of early breast cancer patients
    Speech, Image Processing and Neural Networks, 1994. Proceedings, ISSIPNN '94., 1994 International Symposium on; 05/1994
  • P Robbins · J Papadimitriou ·
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    ABSTRACT: Glandular differentiation in peripheral nerve sheath neoplasms is a rare but well recognised phenomenon, believed to represent the least common of the various forms of heterologous differentiation which may occur in tumours of peripheral nerve. This group of tumours--the 'glandular peripheral nerve sheath neoplasms'--are the subject of this short review. The majority of glandular peripheral nerve sheath neoplasms arise in patients with von Recklinghausen's disease and follow a malignant course, but both benign and sporadic forms have now been described. Neither the presence nor the appearance of the glandular foci are believed to influence patient outcome. Predictions of likely biologic behaviour are best based upon an assessment of the nature of the accompanying spindle cell stroma. Glandular peripheral nerve sheath neoplasms must be distinguished from various tumours of soft tissue which may share similar histological features e.g. synovial sarcoma and the epitheloid nerve sheath tumours. Immunohistochemistry and ultrastructural examination may aid in this regard, and have also contributed to our understanding of the nature and origin of the glandular structures, though questions regarding their histogenic origins remain somewhat controversial.
    Pathology - Research and Practice 05/1994; 190(4):412-5. DOI:10.1016/S0344-0338(11)80418-8 · 1.40 Impact Factor

Publication Stats

589 Citations
32.84 Total Impact Points


  • 1995-2001
    • University of Western Australia
      Perth City, Western Australia, Australia
  • 2000
    • The Chinese University of Hong Kong
      • Department of Orthopaedics and Traumatology
      Hong Kong, Hong Kong
  • 1994-1999
    • Sir Charles Gairdner Hospital
      Perth City, Western Australia, Australia