Publications by authors named "Amy Jamieson"

11 Publications

  • Page 1 of 1

Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique.

Int J Gynecol Cancer 2022 Aug 1;32(8):977-985. Epub 2022 Aug 1.

Division of Gynecologic Pathology, University of Leipzig, Leipzig, Germany.

Objectives: Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.

Methods: In this retrospective cohort study, 68 cases treated by vulvar field resection were identified from the Leipzig School of Radical Pelvic Surgery. Immunohistochemistry for p16 and p53 was performed at three different institutions and evaluated independently by seven pathologists and two trainees. Tumors were classified into one of four groups: HPV associated, HPV independent p53 wild type, HPV independent p53 abnormal, and indeterminate. Selected cases were further interrogated by (HPV RNA in situ hybridization, sequencing).

Results: Final subclassification yielded 22 (32.4%) HPV associated, 41 (60.3%) HPV independent p53 abnormal, and 5 (7.3%) HPV independent p53 wild type tumors. Interobserver agreement (overall Fleiss' kappa statistic) for the four category classification was 0.74. No statistically significant differences in clinical outcomes between HPV associated and HPV independent vulvar squamous cell carcinoma were observed.

Conclusion: Interobserver reproducibility of vulvar squamous cell carcinoma subclassification based on p16 and p53 immunohistochemistry may support routine use in clinical practice. Vulvar field resection surgery showed no significant difference in clinical outcomes when stratified based on HPV status.
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http://dx.doi.org/10.1136/ijgc-2021-003251DOI Listing
August 2022

Molecular classification in endometrial cancer: Opportunities for precision oncology in a changing landscape.

Cancer 2022 08 3;128(15):2853-2857. Epub 2022 Jun 3.

Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada.

Endometrial carcinoma (EC) classification and risk stratification have undergone a global transformation in the last decade, shifting from a reliance on poorly reproducible histomorphological parameters such as grade and histotype, toward a molecular classification that is consistent and biologically informative. Molecular classification enables reliable categorization of ECs, provides prognostic information, and is now beginning to drive clinical management, including surgery and adjuvant therapy. Within this framework, we now have the ability to further refine both the prognostic and predictive value of molecular classification. As we move toward the routine implementation of this classification system as a stratification tool for research, clinical trials, and patient care, it is imperative that access to these tests be equitable. Furthermore, continued education will be critical for patients and providers to understand the value that this molecular information provides.
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http://dx.doi.org/10.1002/cncr.34328DOI Listing
August 2022

Endometrial carcinoma molecular subtype correlates with the presence of lymph node metastases.

Gynecol Oncol 2022 05 2;165(2):376-384. Epub 2022 Mar 2.

Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, Canada. Electronic address:

Background: The role of lymph node assessment/dissection (LND) in endometrial cancer (EC) has been debated for decades, with significant practice variation between centers. Molecular classification of EC provides prognostic information and can be accurately performed on preoperative endometrial biopsies. We assessed the association between molecular subtype and lymph node metastases (LNM) in order to determine if this tool could be used to stratify surgical decision making.

Methods: All EC patients undergoing primary staging surgery with planned complete pelvic +/- para-aortic LND from a single institution in the 2015 calendar year were identified, with clinicopathological and outcome data assessed in the context of retrospectively assigned molecular classification.

Results: 172 patients were included. Molecular classification of the total cohort showed 21 POLEmut (12.2%), 47 MMRd (27.3%), 74 NSMP (43.1%), and 30 p53abn (17.4%) ECs. Complete pelvic +/- para-aortic LND was performed in 171 of 172 patients, and LNM were found in 31/171 (18.1%). This included macrometastases (19/31), micrometastases (5/31), and isolated tumour cells (ITCs) (7/31). LNM were pelvic only in 83.9%, and pelvic plus para-aortic in 16.1%. There were no isolated para-aortic LNM. Molecular subtype was significantly associated with LNM (p = 0.004). There was a strong association between the presence of LNM and p53abn EC (nodal involvement in 44.8% of cases), with LNM detected in 14.2% of POLEmut, 14.9% of MMRd, and 10.8% of NSMP EC. On multivariate analysis, molecular subtype and preoperative CA 125 > 25 were significantly associated with LNM (p = 0.021 and p = 0.022 respectively) but preoperative grade and histotype were not (p = 0.24).

Conclusion: EC molecular subtype is significantly associated with the presence of LNM. As molecular classification can be obtained on preoperative diagnostic specimens, this information can be used to guide surgical treatment planning and may reduce the cost and morbidity of unnecessary lymph node staging in EC care.
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http://dx.doi.org/10.1016/j.ygyno.2022.01.025DOI Listing
May 2022

A Systematic Review of Risk Factors for Development, Recurrence, and Progression of Vulvar Intraepithelial Neoplasia.

J Low Genit Tract Dis 2022 Apr;26(2):140-146

British Columbia Centre for Vulvar Health, Vancouver, Canada.

Objective: Vulvar intraepithelial neoplasia (VIN) is a premalignant condition with high recurrence rates despite treatment. Vulvar intraepithelial neoplasia develops through separate etiologic pathways relative to the presence or absence of human papillomavirus (HPV) and TP53 mutations. This systematic review was conducted (1) to identify historical risk factors for the development, recurrence, and progression of VIN and (2) to critique these risk factors in the context of advances made in the stratification of VIN based on HPV or TP53 status.

Materials And Methods: A systematic search was performed on MEDLINE, Embase, Cochrane Database, PsychInfo, and CINAHL from inception to July 5, 2021. Three gynecologic oncologists independently evaluated the eligibility of studies based on predetermined inclusion and exclusion criteria, abstracted data, and then analyzed the relevant data.

Results: A total of 1,969 studies (involving 6,983 patients) were identified. Twenty-nine studies met inclusion criteria. The quality of evidence was low; primarily level 2b (Oxford Centre for Evidence-Based Medicine). Risk factors associated with the development of VIN include: smoking and coexisting vulvar dermatoses. Risk factors associated with recurrence include: smoking, multifocal disease, and positive surgical margins. Recent studies identified the presence of differentiated VIN/TP53 mutation as the most significant risk factor for both VIN recurrence and malignant progression.

Conclusions: The current body of evidence consists primarily of small retrospective observational studies. Well-designed retrospective case-control series and/or prospective observational studies are urgently needed. Ideally, future studies will collect standardized data regarding associated risk factors and stratify women with VIN based on HPV and TP53 status.
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http://dx.doi.org/10.1097/LGT.0000000000000662DOI Listing
April 2022

Variation in practice in endometrial cancer and potential for improved care and equity through molecular classification.

Gynecol Oncol 2022 05 1;165(2):201-214. Epub 2022 Mar 1.

Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, Canada. Electronic address:

Objectives: We measured the variation in practice across all aspects of endometrial cancer (EC) management and assessed the potential impact of implementation of molecular classification.

Methods: Centers from across Canada provided representative tumor samples and clinical data, including preoperative workup, operative management, hereditary cancer program (HCP) referrals, adjuvant therapy, surveillance and outcomes, for all EC patients diagnosed in 2016. Tumors were classified into the four ProMisE molecular subtypes.

Results: A total of 1336 fully evaluable EC patients were identified from 10 tertiary cancer centers (TC; n = 1022) and 19 community centers (CC; n = 314). Variation of surgical practice across TCs was profound (14-100%) for lymphadenectomy (LND) (mean 57% Gr1/2, 82% Gr3) and omental sampling (20% Gr1/2, 79% Gr3). Preoperative CT scans were inconsistently obtained (mean 32% Gr1/2, 51% Gr3) and use of adjuvant chemo or chemoRT in high risk EC ranged from 0-55% and 64-100%, respectively. Molecular subtyping was performed retrospectively and identified 6% POLEmut, 28% MMRd, 48% NSMP and 18% p53abn ECs, and was significantly associated with survival. Within patients retrospectively diagnosed with MMRd EC only 22% had been referred to HCP. Of patients with p53abn EC, LND and omental sampling was not performed in 21% and 23% respectively, and 41% received no chemotherapy. Comparison of management in 2016 with current 2020 ESGO/ESTRO/ESP guidelines identified at least 26 and 95 patients that would have been directed to less or more adjuvant therapy, respectively (10% of cohort).

Conclusion: Molecular classification has the potential to mitigate the profound variation in practice demonstrated in current EC care, enabling reproducible risk assessment, guiding treatment and reducing health care disparities.
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http://dx.doi.org/10.1016/j.ygyno.2022.02.001DOI Listing
May 2022

The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer.

Ther Adv Med Oncol 2021 14;13:17588359211035959. Epub 2021 Aug 14.

Department of Gynaecology and Obstetrics, Division of Gynaecologic Oncology, University of British Columbia, 2775 Laurel St, Vancouver, BC V6L-1Z5, Canada.

Following the discovery of the four molecular subtypes of endometrial cancer (EC) by The Cancer Genome Atlas (TCGA) in 2013, subsequent studies used surrogate markers to develop and validate a clinically relevant EC classification tool to recapitulate TCGA subtypes. Molecular classification combines focused sequencing () and immunohistochemistry (mismatch repair and p53 proteins) to assign patients with EC to one of four molecular subtypes: mut, MMRd, p53abn and NSMP (no specific molecular profile). Unlike histopathological evaluation, the molecular subtyping of EC offers an objective and reproducible classification system that has been shown to have prognostic value and therapeutic implications. It is an exciting time in EC care where we have moved beyond treatment based on histomorphology alone, and molecular classification will now finally allow assessment of treatment efficacy within biologically similar tumours. It is now recommended that molecular classification should be considered for all ECs, and should be performed routinely in all high grade tumours. It is also recommended to incorporate molecular classification into standard pathology reporting and treatment decision-making algorithms. In this review, we will discuss how the molecular classification of EC can be used to guide both conventional and targeted therapy in this new molecular era.
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http://dx.doi.org/10.1177/17588359211035959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366203PMC
August 2021

p53abn Endometrial Cancer: understanding the most aggressive endometrial cancers in the era of molecular classification.

Int J Gynecol Cancer 2021 06 15;31(6):907-913. Epub 2021 Feb 15.

Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia, Vancouver, British Columbia, Canada

Over the past decade, our understanding of endometrial cancer has changed dramatically from the two-tiered clinicopathologic classification system of type I and type II endometrial cancer through to the four distinct molecular subtypes identified by The Cancer Genome Atlas (TCGA) in 2013. In both systems there is a small subset of endometrial cancers (serous histotype/high numbers of somatic copy number abnormalities) that account for a disproportionately high percentage of endometrial cancer related deaths. This subset can be identified in routine clinical practice by first identifying the approximately one-third of endometrial cancers that are either ultramutated/mut tumors, with pathogenic mutations in the exonuclease domain of , or hypermutated/MMRd tumors, with loss of DNA mismatch repair. Immunostaining for p53 stratifies the remaining endometrial cancers into those with wild-type staining pattern and those with mutant pattern staining (p53abn endometrial cancer). This latter group of p53abn endometrial cancer is the subject of this review. Most p53abn endometrial cancers are serous type and high grade, but it also includes other histotypes and lower grade tumors, and has consistently been associated with the poorest clinical outcomes. Although it only accounts for 15% of all endometrial cancer cases, it is responsible for 50-70% of endometrial cancer mortality. A better understanding of the molecular alterations in the p53abn subgroup, beyond the ubiquitous and definitional mutations, is required so we can identify better treatments for these most aggressive endometrial cancers. Recent evidence has shown improved survival outcomes with the addition of chemotherapy compared with radiation alone in p53abn endometrial cancers. Opportunities for targeted therapy for p53abn endometrial cancers also exist with a proportion of p53abn endometrial cancers known to have homologous recombination deficiency (HRD) or human epidermal growth factor 2 (HER2) overexpression/amplification. This review will provide an overview of our current understanding of p53abn endometrial cancer.
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http://dx.doi.org/10.1136/ijgc-2020-002256DOI Listing
June 2021

Response to: Cervical cancer in women under 25 years of age in Queensland, Australia: To what extent is the diagnosis made by screening cytology?

Aust N Z J Obstet Gynaecol 2018 06;58(3):E5-E6

Department of Gynaecologic Oncology, Westmead Hospital, Sydney, NSW, Australia.

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http://dx.doi.org/10.1111/ajo.12793DOI Listing
June 2018

Subtypes of stage IV ovarian cancer; response to treatment and patterns of disease recurrence.

Gynecol Oncol 2017 08 23;146(2):273-278. Epub 2017 May 23.

Department of Gynaecologic Oncology, Christchurch Women's Hospital, 2 Riccarton Avenue, Christchurch 8140, New Zealand; University of Otago, Department of Gynaecologic Oncology, Christchurch Women's Hospital, 2 Riccarton Avenue, Christchurch 8140, New Zealand; Department of Gynaecologic Oncology, Auckland City Hospital, 2 Park Road, Grafton, Auckland 1023, New Zealand; Department of Gynaecologic Oncology, Wellington Hospital, Riddiford Street, Newtown, Wellington 6021, New Zealand; Department of Gynaecologic Oncology, Christchurch Women's Hospital, 2 Riccarton Avenue, Christchurch 8140, New Zealand.

Background: To compare three different patterns of stage IV epithelial ovarian cancer; pleural effusion, parenchymal metastases and extra-abdominal lymph node metastases with treatment response and pattern of disease recurrence, and correlate treatment modality with outcome.

Methods: Retrospective analysis of FIGO stage IV epithelial ovarian cancer diagnosed between 2008 and 2012 in three gynaecologic oncology centres in New Zealand.

Results: 124 patients were analysed, 58 had pleural effusions, 38 parenchymal metastases, and 28 extra-abdominal lymph nodes. There was no significant difference in overall survival between these three groups. The most common site of first or any recurrence in all three groups was the abdomen with only a small number of recurrences arising in extra-abdominal sites. When looking at treatment modality, 13% had primary debulking surgery, 47% had neoadjuvant chemotherapy with interval debulking surgery, and 40% never had surgery. Overall survival was highest in patients with no residual abdominal disease after surgery.

Conclusion: The site of extra-abdominal disease did not alter prognosis or pattern of disease recurrence in stage IV epithelial ovarian cancer, with most recurrences in the abdomen suggesting controlling abdominal disease with surgery may be important in all stage IV disease.
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http://dx.doi.org/10.1016/j.ygyno.2017.05.023DOI Listing
August 2017

Surgery and Obstetric Care are Highly Cost-Effective Interventions in a Sub-Saharan African District Hospital: A Three-Month Single-Institution Study of Surgical Costs and Outcomes.

World J Surg 2016 Jan;40(1):14-20

Background: The Lancet recently sponsored a commission examining the role of surgery in global health. There is a paucity of published information on the cost-effectiveness of surgery in low- and middle-income countries, a key metric in the prioritisation of limited resources.

Methods: All patients undergoing emergency laparotomy, elective and emergency inguinal hernia repair, elective and emergency caesarean section, amputation, fracture manipulation, or fracture fixation over a 3 months period in a single district African hospital were assessed. World Health Organisation global burden of disease (GBD) methodology was used to calculate the disability-adjusted life years (DALYs) saved for each patient (using global and local life expectancy). Fully loaded costs were calculated for each patient’s care and providing the overall surgical service. Cost-effectiveness was calculated in year 2012 US$ per DALY saved for each procedure and overall.

Results: A total of 428 patients were included, with an overall cost-effectiveness of $10.70 per DALY averted. The cost-effectiveness of individual procedures (global life expectancy) was: Amputation—$17.66; Emergency caesarean section—$7.42; Elective caesarean section—$20.50; Emergency laparotomy—$8.62; Elective hernia repair—$15.26; Emergency hernia repair—$4.36; Fracture/dislocation reduction—$69.03; Fracture/dislocation fixation—$225.89.

Conclusions: Surgery is a highly cost-effective healthcare measure in the setting of an African district hospital. The presented outcomes demonstrate that surgery is on a par with better-recognised and funded interventions such as HIV anti-retrovirals, malaria prevention and diarrhoea treatment. There are recognised limitations with the GBD methodology used here; however, this remains the best way to investigate the cost-effectiveness of health interventions. This study provides useful information on an, at present, under-studied field.
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http://dx.doi.org/10.1007/s00268-015-3271-6DOI Listing
January 2016

Perianal abscess in children: aiming for optimal management.

ANZ J Surg 2012 Jan-Feb;82(1-2):60-2. Epub 2012 Jan 9.

Department of Paediatric Surgery, Christchurch Hospital, Christchurch, New Zealand.

Background: Perianal abscess is common in infants and children, yet the optimal surgical management is argued: incision and drainage alone is a simple procedure but is associated with a much higher recurrence rate than incision and drainage with simultaneous laying open of the associated fistula. This retrospective review established the institutional recurrence rate and its close association with how the fistula was managed at the initial operation.

Methods: A retrospective review of all children requiring an operation for a perianal abscess over a 13-year period from 1996 to 2009 was performed. Data were compared with published series.

Results: A fistula was sought in 89 of 91 (98%) patients, and identified in 66 (73%). Recurrence occurred in 5/66 (8%) in whom a fistula was identified at the initial operation, compared with 6/25 (24%) (P = 0.06) in whom a fistula was not identified.

Conclusion: Recurrence of perianal infection is influenced by whether a fistula was identified and laid open at the initial operation. The recurrence rate is higher when the abscess is treated with incision and drainage alone. Given the ease with which most fistulae may be identified, and laid open without morbidity, optimal treatment involves drainage of the abscess and laying open of the fistulous tract.
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http://dx.doi.org/10.1111/j.1445-2197.2011.05941.xDOI Listing
August 2012
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