Kay Lawson - Academia.edu (original) (raw)

Papers by Kay Lawson

British Journal of Cancer

BACKGROUND: Intratumoural T-cell infiltrate intensity cortes wrelaith clinical outcome in stage I... more BACKGROUND: Intratumoural T-cell infiltrate intensity cortes wrelaith clinical outcome in stage II/III colorectal cancer (CRC). We aimed to determine whether this association varies across this heterogeneous group. METHODS: We performed a pooled analysis of 1804 CRCs from the QUASAR2 and VICTOR trials. Intratumoural CD8 + and CD3 + densities were quantified by immunohistochemistry in tissue microarray (TMA) cores, and their association with clinical outcome analysed by Cox regression. We validated our results using publicly available gene expression data in a pooled analysis of 1375 CRCs from seven independent series. RESULTS: In QUASAR2, intratumoural CD8 + was a stronger predictor of CRC recurrence than CD3 + and showed similar discriminative ability to both markers in combination. Pooled multivariable analysis of both trials showed increasing CD8 + density was associated with reduced recurrence risk independent of confounders including DNA mismatch repair deficiency, POLE mutation and chromosomal instability (multivariable hazard ratio [HR] for each two-fold increase = 0.92, 95%CI = 0.87-0.97, P = 3.6 × 10 −3 ). This association was not uniform across risk strata defined by tumour and nodal stage: absent in low-risk (pT3,N0) cases (HR = 1.03, 95%CI = 0.87-1.21, P = 0.75), modest in intermediate-risk (pT4,N0 or pT1-3,N1-2) cases (HR = 0.92, 95%CI = 0.86-1.0, P = 0.046) and strong in high-risk (pT4,N1-2) cases (HR = 0.87, 95%CI = 0.79-0.97, P = 9.4 × 10 −3 ); P INTERACTION = 0.090. Analysis of tumour CD8A expression in the independent validation cohort revealed similar variation in prognostic value across risk strata (P INTERACTION = 0.048). CONCLUSIONS: The prognostic value of intratumoural CD8 + cell infiltration in stage II/III CRC varies across tumour and nodal risk strata.

Journal of Clinical Oncology

British Journal of Plastic Surgery, 2002

Hemifacial microsomia describes a congenital orofacial malformation in which there is insufficien... more Hemifacial microsomia describes a congenital orofacial malformation in which there is insufficient or disrupted development of the mandible affecting one side of the face. The aetiology of this condition remains unclear, but it has been postulated that twins (predominantly monozygotic) are more liable to be affected than singletons. This study investigates the incidence of multiple births amongst a large number of affected individuals and their families. Data were collected on 145 individuals with hemifacial microsomia and microtia, using postal questionnaires and interviews in a hospital setting. These data were compared with the mean age-standardised twin maternity prevalence for England and Wales between 1975 and 1995 of 1.06% and the triplet maternity prevalence for England and Wales for 1995 of 0.034% (a multiple maternity being where more than one baby is born, either alive or stillborn). The prevalence of twin maternities amongst the affected individuals was 3.96% (P > 0.05) and amongst their siblings it was 4.02% (P < 0.02). There was also an excess of twins in the rest of the family groups, predominantly due to a stronger history of twinning on the maternal side. As there were more twins amongst the affected individuals than in the general population, it seems likely that whatever the aetiology of hemifacial microsomia and microtia, the presence of a co-twin (or co-triplets) may make the causal event, or series of causal events, more likely to occur. This study supports the hypothesis that hemifacial microsomia and microtia are in some way linked to multiple births. Analysis of this link may provide new directions for research into the aetiology of a variety of congenital defects. 9 2002 The British Association of Plastic Surgeons

The American Journal of Surgical Pathology, 2011

We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distincti... more We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distinctive histomorphologic features and characterized by a recurrent fusion gene, that appear to represent a distinct tumor entity at this site. The patients [7 female, 3 male; aged 27 to 67 y (mean, 45 y)] presented with local or systemic symptoms (n=5), symptoms from cerebral metastasis (1), or incidentally (2). Follow-up of 6 patients showed that 1 with brain metastasis died shortly after primary tumor resection, 1 developed a renal metastasis but is alive and well, and 4 are disease free after 1 to 15 years. All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 8 and ranged from 1.5 to 4 cm. Microscopically, they were lobulated and composed of cords of polygonal, spindle, or stellate cells within myxoid stroma, morphologically reminiscent of extraskeletal myxoid chondrosarcoma. Four cases showed no or minimal atypia, 6 showed focal pleomorphism, and 5 had necrosis. Mitotic indices varied, with most tumors not exceeding 5/10 high-power fields. Tumors were immunoreactive for only vimentin and weakly focal for epithelial membrane antigen. Of 9 tumors, 7 were shown to harbor a specific EWSR1-CREB1 fusion by reverse transcription-polymerase chain reaction and direct sequencing, with 7 of 10 showing EWSR1 rearrangement by fluorescence in situ hybridization. This gene fusion has been described previously in 2 histologically and behaviorally different sarcomas: clear cell sarcoma-like tumors of the gastrointestinal tract and angiomatoid fibrous histiocytomas; however, this is a novel finding in tumors with the morphology we describe and that occur in the pulmonary region.

The Lancet Gastroenterology & Hepatology, 2016

British Journal of Cancer

BACKGROUND: Intratumoural T-cell infiltrate intensity cortes wrelaith clinical outcome in stage I... more BACKGROUND: Intratumoural T-cell infiltrate intensity cortes wrelaith clinical outcome in stage II/III colorectal cancer (CRC). We aimed to determine whether this association varies across this heterogeneous group. METHODS: We performed a pooled analysis of 1804 CRCs from the QUASAR2 and VICTOR trials. Intratumoural CD8 + and CD3 + densities were quantified by immunohistochemistry in tissue microarray (TMA) cores, and their association with clinical outcome analysed by Cox regression. We validated our results using publicly available gene expression data in a pooled analysis of 1375 CRCs from seven independent series. RESULTS: In QUASAR2, intratumoural CD8 + was a stronger predictor of CRC recurrence than CD3 + and showed similar discriminative ability to both markers in combination. Pooled multivariable analysis of both trials showed increasing CD8 + density was associated with reduced recurrence risk independent of confounders including DNA mismatch repair deficiency, POLE mutation and chromosomal instability (multivariable hazard ratio [HR] for each two-fold increase = 0.92, 95%CI = 0.87-0.97, P = 3.6 × 10 −3 ). This association was not uniform across risk strata defined by tumour and nodal stage: absent in low-risk (pT3,N0) cases (HR = 1.03, 95%CI = 0.87-1.21, P = 0.75), modest in intermediate-risk (pT4,N0 or pT1-3,N1-2) cases (HR = 0.92, 95%CI = 0.86-1.0, P = 0.046) and strong in high-risk (pT4,N1-2) cases (HR = 0.87, 95%CI = 0.79-0.97, P = 9.4 × 10 −3 ); P INTERACTION = 0.090. Analysis of tumour CD8A expression in the independent validation cohort revealed similar variation in prognostic value across risk strata (P INTERACTION = 0.048). CONCLUSIONS: The prognostic value of intratumoural CD8 + cell infiltration in stage II/III CRC varies across tumour and nodal risk strata.

Journal of Clinical Oncology

British Journal of Plastic Surgery, 2002

Hemifacial microsomia describes a congenital orofacial malformation in which there is insufficien... more Hemifacial microsomia describes a congenital orofacial malformation in which there is insufficient or disrupted development of the mandible affecting one side of the face. The aetiology of this condition remains unclear, but it has been postulated that twins (predominantly monozygotic) are more liable to be affected than singletons. This study investigates the incidence of multiple births amongst a large number of affected individuals and their families. Data were collected on 145 individuals with hemifacial microsomia and microtia, using postal questionnaires and interviews in a hospital setting. These data were compared with the mean age-standardised twin maternity prevalence for England and Wales between 1975 and 1995 of 1.06% and the triplet maternity prevalence for England and Wales for 1995 of 0.034% (a multiple maternity being where more than one baby is born, either alive or stillborn). The prevalence of twin maternities amongst the affected individuals was 3.96% (P > 0.05) and amongst their siblings it was 4.02% (P < 0.02). There was also an excess of twins in the rest of the family groups, predominantly due to a stronger history of twinning on the maternal side. As there were more twins amongst the affected individuals than in the general population, it seems likely that whatever the aetiology of hemifacial microsomia and microtia, the presence of a co-twin (or co-triplets) may make the causal event, or series of causal events, more likely to occur. This study supports the hypothesis that hemifacial microsomia and microtia are in some way linked to multiple births. Analysis of this link may provide new directions for research into the aetiology of a variety of congenital defects. 9 2002 The British Association of Plastic Surgeons

The American Journal of Surgical Pathology, 2011

We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distincti... more We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distinctive histomorphologic features and characterized by a recurrent fusion gene, that appear to represent a distinct tumor entity at this site. The patients [7 female, 3 male; aged 27 to 67 y (mean, 45 y)] presented with local or systemic symptoms (n=5), symptoms from cerebral metastasis (1), or incidentally (2). Follow-up of 6 patients showed that 1 with brain metastasis died shortly after primary tumor resection, 1 developed a renal metastasis but is alive and well, and 4 are disease free after 1 to 15 years. All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 8 and ranged from 1.5 to 4 cm. Microscopically, they were lobulated and composed of cords of polygonal, spindle, or stellate cells within myxoid stroma, morphologically reminiscent of extraskeletal myxoid chondrosarcoma. Four cases showed no or minimal atypia, 6 showed focal pleomorphism, and 5 had necrosis. Mitotic indices varied, with most tumors not exceeding 5/10 high-power fields. Tumors were immunoreactive for only vimentin and weakly focal for epithelial membrane antigen. Of 9 tumors, 7 were shown to harbor a specific EWSR1-CREB1 fusion by reverse transcription-polymerase chain reaction and direct sequencing, with 7 of 10 showing EWSR1 rearrangement by fluorescence in situ hybridization. This gene fusion has been described previously in 2 histologically and behaviorally different sarcomas: clear cell sarcoma-like tumors of the gastrointestinal tract and angiomatoid fibrous histiocytomas; however, this is a novel finding in tumors with the morphology we describe and that occur in the pulmonary region.

The Lancet Gastroenterology & Hepatology, 2016