P Robbins

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

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Publications (42)130.08 Total impact

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    ABSTRACT: Summary Expression levels of nm23-H1 were evaluated in a variety of normal, benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group. Some special tumor types known to metastasize infrequently (tubular, tubulo-lobular carcinoma) had low levels of expression, whilst others (colloid carcinoma) exhibited high levels of expression. Comparison of samples of primary tumor, surrounding normal breast and metastatic node deposits in individual patients showed no clear trends in gene expression between these tissue types. The validity of nm23-H1 as a marker of metastatic potential is questioned on the basis of these results. The higher levels of expression observed in malignant tissue suggest that nm23-H1 may be involved in tumorigenesis, but clear evidence for this, and the mechanisms by which the gene may influence tumor biology, remain to be determined.
    Pathology 07/2009; 26(4):423-428. · 2.66 Impact Factor
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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. · 2.28 Impact Factor
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    ABSTRACT: To examine whether p53 tumour suppressor gene alterations can be used to predict tumour response to pre-operative chemo-radiation in locally advanced rectal cancer in terms of reduction in tumour size and local failure. p53 alterations were studied in pre-treatment biopsy specimens of rectal carcinomas from 48 patients by immunohistochemistry (IHC) and polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) gene mutation analysis. Pre-operative pelvic radiotherapy was delivered with four fields, 45 Gy to the ICRU point in 25 fractions over 5 weeks. A radio-sensitising dose of 5-fluorouracil (500 mg/m(2)) was delivered concurrently for 6 days of the 5-week schedule (days 1, 2, 3 and days 22, 23 and 24). Total meso-rectal excision was planned 4 to 6 weeks from completion of pre-operative treatment. Response to therapy was assessed by macroscopic measurement of the surgical specimen by a pathologist who was unaware of the pre-treatment tumour size or of the p53 status. IHC evidence of p53 protein accumulation was found in 40% of tumours, p53 gene mutation in 35% and p53 alteration (either or both changes) in 46%. The average reduction in tumour size was 53% in the group with 'wild-type' p53 (IHC-/SSCP-) and 63% in the group with altered p53 (either IHC+ or SSCP+; P=0.18). No significant differences in tumour size reduction or local failure were observed in the groups with p53 overexpression or p53 mutation compared with normal. p53 alteration detected by IHC or SSCP analysis is not a clinically useful predictor of local response to pre-operative adjuvant therapy in advanced rectal carcinoma.
    Radiotherapy and Oncology 09/2000; 56(2):239-44. · 4.52 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. · 2.84 Impact Factor
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    ABSTRACT: Improved prognostic and predictive markers in breast cancer management would help considerably in therapeutic decision making, particularly in patients with early-stage breast cancer. Tumor factors currently used for prognostication and management decisions are tumor size, histologic type and grade, axillary lymph node status, and estrogen receptor content. The discovery of various somatic genetic alterations in breast cancer has raised the possibility that these may provide additional and independent prognostic and predictive information. Alterations of the p53 tumor suppressor gene in particular have received the most attention as potential prognostic and predictive factors. In multivariate analysis, p53 gene mutation is consistently associated with a two- to threefold increased risk of relapse and death from breast cancer. One of the major reasons preventing the introduction of p53 mutation as a routine marker to assist in therapeutic decision making is the lack of a simple, reproducible, and inexpensive assay. In the present study the authors optimized a polymerase chain reaction-based mutation screening method, fluorescence-single strand conformation polymorphism (F-SSCP), that allows p53 status to be assessed accurately and reproducibly in routinely handled, formalin-fixed and paraffin-embedded tumor specimens. The frequency of p53 mutation observed using F-SSCP in a consecutive series of invasive ductal breast carcinomas was 17% (28/164). The authors propose that the prognostic and predictive values of p53 mutation in breast cancer should be further evaluated in prospective, randomized studies using this standardized technique.
    Diagnostic Molecular Pathology 04/2000; 9(1):20-5. · 1.86 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. · 2.49 Impact Factor
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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.
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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. · 0.51 Impact Factor
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    ABSTRACT: The aim of our study was to examine the prognostic significance of p53 protein accumulation and gene mutation in a series of 116 gastric carcinomas from a low incidence population. Formalin-fixed, paraffin-embedded tumour sections were used to investigate p53 protein accumulation by immunostaining with monoclonal antibody (MAb) DO-7 and p53 gene mutation by single-strand conformation polymorphism analysis of exons 5-8. Nuclear p53 accumulation was detected in 23% of tumours and mutation in 28%. Concordance between the 2 alterations was observed in 73% of cases. p53 protein accumulation was more frequent in tumours with lymph node metastasis, while p53 mutations were more frequent in tumours from older patients. The histopathological parameters of depth of invasion, grade and histological type showed no significant associations with either p53 alteration. In univariate analysis, both alterations were associated with significantly shortened patient survival. The 5-year survival rate for patients with a p53 mutation was 9% compared to 42% for those without a mutation. In multivariate analysis adjusted for the other histopathological parameters, p53 gene mutation but not immunohistochemically-detected p53 protein accumulation was an independent prognostic indicator of poor survival in gastric carcinoma. © 1996 Wiley-Liss, Inc.
    International Journal of Cancer 12/1998; 69(3):200 - 204. · 6.20 Impact Factor
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    ABSTRACT: We examined the association between mutation of the p53 gene and survival in a large cohort of breast cancer patients. Using a rapid, non-isotopic single-strand conformation polymorphism (SSCP) method we screened for mutations in exons 4–10 of the p53 gene in 375 primary breast cancers from patients with a median follow-up of 57 months. Mutations were found in 19% of tumours. Statistically significant associations were found between p53 mutation and histological grade, hormone receptor status, ploidy and S-phase fraction. No association was found between p53 mutation and axillary lymph node involvement, histological type, tumour size, vascular invasion or patient age. In univariate survival analysis, p53 mutation was strongly associated with poor prognosis. This was maintained in the lymph node-negative and hormone receptor-positive patient subgroups. In multivariate analysis, p53 mutation was associated with poor survival independent of lymph node status, estrogen receptor status and S-phase fraction. Our results demonstrate the feasibility of using a rapid and simple polymerase chain reaction-SSCP screening procedure to detect p53 gene mutation in breast cancer for the provision of prognostic information. Int. J. Cancer 74:642–647, 1997.© 1997 Wiley-Liss, Inc.
    International Journal of Cancer 12/1998; 74(6):642 - 647. · 6.20 Impact Factor
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    ABSTRACT: We examined the association between mutation of the p53 gene and survival in a large cohort of breast cancer patients. Using a rapid, non-isotopic single-strand conformation polymorphism (SSCP) method we screened for mutations in exons 4-10 of the p53 gene in 375 primary breast cancers from patients with a median follow-up of 57 months. Mutations were found in 19% of tumours. Statistically significant associations were found between p53 mutation and histological grade, hormone receptor status, ploidy and S-phase fraction. No association was found between p53 mutation and axillary lymph node involvement, histological type, tumour size, vascular invasion or patient age. In univariate survival analysis, p53 mutation was strongly associated with poor prognosis. This was maintained in the lymph node-negative and hormone receptor-positive patient subgroups. In multivariate analysis, p53 mutation was associated with poor survival independent of lymph node status, estrogen receptor status and S-phase fraction. Our results demonstrate the feasibility of using a rapid and simple polymerase chain reaction-SSCP screening procedure to detect p53 gene mutation in breast cancer for the provision of prognostic information.
    International Journal of Cancer 01/1998; 74(6):642-7. · 6.20 Impact Factor
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    ABSTRACT: Case-control methodology was used to evaluate the significance of vascularity in small breast carcinomas with regard to the presence or absence of axillary lymph node metastases. Vascularity was assessed in 32 axillary node positive primary breast tumours (LN+ve) less than 2 cm in size and compared with 56 control axillary node negative primary tumours (LN-ve), which were matched for histological type and grade and tumour size. This study design employed computer-assisted video analysis (CAVA) to assess the total blood vessel perimeter (BVP), total blood vessel area (BVA), and total blood vessel density (BVD) throughout a tissue section that encompassed an entire cross section of the tumour and its immediate periphery. The BVA and BVD in these tumours were not significantly different between LN+ve and LN-ve groups. The LN-ve carcinomas had, on average, a significantly (P<0.05) higher total BVP (3355 microm/mm2) than LN+ve tumours (2771 microm/mm2). 'Hot spot' areas were also independently assessed by two pathologists and the same areas measured by CAVA. A strong correlation (P<0.001) between the two methods of assessment of BVD of the neovascular 'hot spots' was found; however, no association with axillary lymph node metastasis was found using either method of assessment. In conclusion, vascularity assessed by either blood vessel density or blood vessel size in primary invasive breast cancers less than 2 cm in diameter showed no association with axillary lymph node metastasis; in fact a negative association was found with total BVP of whole tumour sections and BVD in 'hot spots' using CAVA. Further, this study has established a computer-assisted method of quantifying vascularity in solid neoplasms and is a positive step towards a standardised approach to this diverse and methodologically variable area.
    Breast Cancer Research and Treatment 01/1998; 47(1):17-27. · 4.47 Impact Factor
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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. · 7.84 Impact Factor
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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.
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    ABSTRACT: Pathology reports and slides were reviewed from 267 mammographically detected impalpable breast lesions, excised after hookwire localisation. There were 182 benign and 85 malignant lesions (benign to malignant ratio of 2.1:1). The invasive cancers tended to be small (mean 13 mm; 50% < or = 10 mm), of low histologic grade (38% Grade I), with a low incidence of lymph node metastases (15%). A high proportion of pure duct carcinoma in situ (DCIS) lesions (21%) was found, and an unusually high proportion of invasive lobular carcinoma (17%). Preoperative fine needle aspiration (FNA) was performed in 95 (36%) cases, including 47 (18%) sampled using sterotactic guidance and 48 (18%) sampled by palpation. The absolute sensitivity of diagnosis of malignancy was 32% and 5% respectively. In 79% of carcinomas further operation was performed, for axillary clearance or re-excision of incompletely excised tumor; this high rate was largely a result of a decision not to use frozen section diagnosis for impalpable lesions and because of the early stages of the development of preoperative needle diagnosis. 58% of invasive cancers, including seven of eight (87.5%) carcinomas with an extensive intraduct component (EIC + ve), and 72% of DCIS were incompletely excised at the first operation. Residual tumor was found in the re-excisions in 26% of EIC - ve invasive carcinomas, 71% of the EIC + ve cases and 56% of DCIS lesions. The malignant lesions had highly favourable prognostic indices. The need for concentration of experience with pre-operative FNA was highlighted. Positive excision margins were a good predictor for residual malignancy, particularly for EIC + ve cases and for DCIS lesions.
    Pathology 03/1997; 29(1):21-7. · 2.66 Impact Factor
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    ABSTRACT: Background: 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.Methods: 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).Results: 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 × 109/L to 84 ± 13 × 109/L for control livers. In comparison for livers stored in UW solution, the platelet count fell from 173 ± 43 × 109/L to 61 ± 14 × 109/L, representing a 64.8% fall, while for those stored in Hartmann's solution, an even more profound fall from 152 ± 36 × 109/L to 19 ± 9 × 109/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.Conclusions: 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.
    ANZ Journal of Surgery 01/1997; 67(7):442-447. · 1.50 Impact Factor
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    ABSTRACT: Immunohistochemical (IHC) detection of p53 protein was compared with the presence of p53 gene mutation in many colorectal (n = 100), breast (n = 92), endometrial (n = 122), and gastric (n = 116) carcinomas. Two commercially available antibodies, DO7 and CM1, were used for IHC analysis of paraffin-embedded tissue sections. Screening for gene mutations in frozen and paraffin-embedded tumor samples was carried out using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The frequency of nuclear staining with DO7 or CM1 for each tumor type, respectively, was colorectal (36%, 23%); breast (15%, 19%); endometrial (21%, 33%); and gastric (23%,-). Overall correlation between the two antibodies for nuclear staining was 90% for the 314 tumors analyzed. Cytoplasmic staining was observed with DO7 in 7% of breast and 5% of gastric carcinomas and with CM1 in 17% of breast and 54% of endometrial carcinomas. p53 gene mutation was found in 39% of colorectal, 28% of breast, 13% of endometrial, and 25% of gastric cancers. The concordance between p53 nuclear overexpression and gene mutation (both positive or both negative) was 68% for colorectal, 79% for breast, 76% for endometrial, and 73% for gastric carcinomas. This study provides further evidence that IHC detection of p53 protein accumulation does not always indicate the presence of a gene mutation and vice versa. Discordant results were observed in approximately 20% to 30% of the tumors studied, highlighting the need for careful characterization of both p53 gene and protein alterations when assessing the relationship between p53 status and tumor behavior.
    Human Pathlogy 11/1996; 27(10):1050-5. · 2.84 Impact Factor
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    ABSTRACT: The aim of our study was to examine the prognostic significance of p53 protein accumulation and gene mutation in a series of 116 gastric carcinomas from a low incidence population. Formalin-fixed, paraffin-embedded tumour sections were used to investigate p53 protein accumulation by immunostaining with monoclonal antibody (MAb) DO-7 and p53 gene mutation by single-strand conformation polymorphism analysis of exons 5-8. Nuclear p53 accumulation was detected in 23% of tumours and mutation in 28%. Concordance between the 2 alterations was observed in 73% of cases. p53 protein accumulation was more frequent in tumours with lymph node metastasis, while p53 mutations were more frequent in tumours from older patients. The histopathological parameters of depth of invasion, grade and histological type showed no significant associations with either p53 alteration. In univariate analysis, both alterations were associated with significantly shortened patient survival. The 5-year survival rate for patients with a p53 mutation was 9% compared to 42% for those without a mutation. In multivariate analysis adjusted for the other histopathological parameters, p53 gene mutation but not immunohistochemically-detected p53 protein accumulation was an independent prognostic indicator of poor survival in gastric carcinoma.
    International Journal of Cancer 07/1996; 69(3):200-4. · 6.20 Impact Factor
  • Human pathology 06/1996; 27(6):618. · 3.03 Impact Factor
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    ABSTRACT: Routine axillary dissection is primarily used as a means of assessing prognosis to establish appropriate treatment plans for patients with primary breast carcinoma. However, axillary dissection offers no therapeutic benefit to node negative patients and patients may incur unnecessary morbidity, including mild to severe impairment of arm motion and lymphedema, as a result. This paper outlines a method of evaluating the probability of harbouring lymph node metastases at the time of initial surgery by assessment of tumour based parameters, in order to provide an objective basis for further selection of patients for treatment or investigation. The novel aspect of this study is the use of Maximum Entropy Estimation (MEE) to construct probabilistic models of the relationship between the risk factors and the outcome. Two hundred and seventeen patients with invasive breast carcinoma were studied. Surgical treatment included axillary clearance in all cases, so that the pathologic status of the nodes was known. Tumour size was found to be significantly correlated (P < 0.001) to the axillary lymph node status in the multivariate anlaysis with age (P = 0.089) and vascular invasion (P = 0.08) marginally correlated. Using the multivariate model constructed, 38 patients were predicted to have risk of nodal metastases lower than 20%, of these only 4 (10%) patients had lymph node metastases. A comparison with the Multivariate Logistic Regression (MLR) was carried out. It was found that the predictive quality of the MEE model was better than that of the MLR model. In view of the small sample size, further verification of this model is required in assessing its practical application to a larger population.
    Breast Cancer Research and Treatment 02/1996; 37(2):135-49. · 4.47 Impact Factor

Publication Stats

899 Citations
130.08 Total Impact Points

Institutions

  • 1992–2001
    • University of Western Australia
      • • School of Surgery
      • • School of Pathology and Laboratory Medicine
      Perth City, Western Australia, Australia
  • 1993–2000
    • Sir Charles Gairdner Hospital
      Perth City, Western Australia, Australia
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia