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Prognostic factors in periampullary adenocarcinoma. A retrospective study over an 11 year period.

Elebro, Jacob LU (2016)
Abstract (Swedish)
Periampullary adenocarcinoma, including pancreatic cancer, has a poor prognosis that has not improved in the
last decades. Therefore, in order to find more effective treatment regimens, it is necessary to gain more insight
into the biology and clinical behaviour of these tumours.
This thesis entails a thorough histopathological characterization of retrospectively collected tumours from a
consecutive cohort of patients with resected periampullary adenocarcinoma, followed by tissue microarray-based
immunohistochemical studies of eight candidate protein biomarkers. Tumours were classified as being of
pancreatobiliary type (PB-type) or intestinal type (I-type), using histological criteria, and all biomarker... (More)
Periampullary adenocarcinoma, including pancreatic cancer, has a poor prognosis that has not improved in the
last decades. Therefore, in order to find more effective treatment regimens, it is necessary to gain more insight
into the biology and clinical behaviour of these tumours.
This thesis entails a thorough histopathological characterization of retrospectively collected tumours from a
consecutive cohort of patients with resected periampullary adenocarcinoma, followed by tissue microarray-based
immunohistochemical studies of eight candidate protein biomarkers. Tumours were classified as being of
pancreatobiliary type (PB-type) or intestinal type (I-type), using histological criteria, and all biomarker analyses
were performed in strata according to morphological type.
In Paper I, histopathological studies showed that a standardized and meticulous protocol for assessment of the
surgical specimens, as well as blind revisions of slides, had impact on the decision on tumour origin, the number
of involved lymph nodes and involved margins.
The biomarker studies in Paper II revealed that expression of the global gene regulator special AT-rich sequencebinding protein 1 (SATB1) was an independent factor of poor prognosis in PB-type tumours. SATB1 expression,
however, also indicated a better response to adjuvant chemotherapy, in particular in I-type tumours. A closely
related protein, SATB2, was found to be expressed in a few tumours only, making it difficult to draw any firm
conclusions on its prognostic value.
In Paper III, biomarker studies on proteins related togemcitabine metabolism revealed that a high ratio between
cytoplasmic and nuclear expression of human protein R (HuR) indicated resistance to chemotherapy in PB-type
tumours. In I-type tumours, high expression of human equilibrative nucleoside transporter 1 (hENT1) was a
favourable prognostic factor and high expression of deoxycytidine kinase (dCK) indicated sensitivity to
chemotherapy.
In Paper IV, biomarker studies on the human epidermal growth factor receptors 1-3 (HER1-3) revealed a potential
negative predictive effect of high EGFR (HER1) expression in relation to adjuvant chemotherapy in PB-type
tumours. Six percent of I-type tumours had high expression of HER2, and gene amplification was confirmed in
assessable cases. In I-type tumours, high expression of HER3 was a favourable prognostic factor, but not
independent of other prognostic factors.
Several of the potentially treatment predictive associations described in this thesis are novel, and may be of
clinical interest if the results can be repeated in other cohorts and if the mechanistic basis is understood. The
results presented here must be however be interpreted with caution, since the cohort is retrospective and many
tests have been made. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor Prydz Gladhaug, Ivar, University of Oslo, Norway. Instiute of Clinical Medicine.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Periampullary adenocarcinoma, Pancreatic cancer, bile duct cancer, ampullary adenocarcinoma, duodenal adenocarcinoma, Immunohistochemestry, prognosis
pages
83 pages
publisher
Lund University, Faculty of Medicine
defense location
Föreläsningssalen, Radiologihuset, plan 3, Skånes universitetssjukhus i Lund.
defense date
2016-05-13 09:15
ISBN
978-91-7619-274-0
language
English
LU publication?
yes
id
ff572b72-284e-442c-a2fb-31fd8d23781b (old id 8872277)
date added to LUP
2016-05-11 09:49:27
date last changed
2016-09-19 08:45:20
@phdthesis{ff572b72-284e-442c-a2fb-31fd8d23781b,
  abstract     = {Periampullary adenocarcinoma, including pancreatic cancer, has a poor prognosis that has not improved in the <br/>last decades. Therefore, in order to find more effective treatment regimens, it is necessary to gain more insight <br/>into the biology and clinical behaviour of these tumours. <br/>This thesis entails a thorough histopathological characterization of retrospectively collected tumours from a <br/>consecutive cohort of patients with resected periampullary adenocarcinoma, followed by tissue microarray-based <br/>immunohistochemical studies of eight candidate protein biomarkers. Tumours were classified as being of <br/>pancreatobiliary type (PB-type) or intestinal type (I-type), using histological criteria, and all biomarker analyses <br/>were performed in strata according to morphological type. <br/>In Paper I, histopathological studies showed that a standardized and meticulous protocol for assessment of the <br/>surgical specimens, as well as blind revisions of slides, had impact on the decision on tumour origin, the number <br/>of involved lymph nodes and involved margins. <br/>The biomarker studies in Paper II revealed that expression of the global gene regulator special AT-rich sequencebinding protein 1 (SATB1) was an independent factor of poor prognosis in PB-type tumours. SATB1 expression, <br/>however, also indicated a better response to adjuvant chemotherapy, in particular in I-type tumours. A closely <br/>related protein, SATB2, was found to be expressed in a few tumours only, making it difficult to draw any firm <br/>conclusions on its prognostic value. <br/>In Paper III, biomarker studies on proteins related togemcitabine metabolism revealed that a high ratio between <br/>cytoplasmic and nuclear expression of human protein R (HuR) indicated resistance to chemotherapy in PB-type <br/>tumours. In I-type tumours, high expression of human equilibrative nucleoside transporter 1 (hENT1) was a <br/>favourable prognostic factor and high expression of deoxycytidine kinase (dCK) indicated sensitivity to <br/>chemotherapy. <br/>In Paper IV, biomarker studies on the human epidermal growth factor receptors 1-3 (HER1-3) revealed a potential <br/>negative predictive effect of high EGFR (HER1) expression in relation to adjuvant chemotherapy in PB-type <br/>tumours. Six percent of I-type tumours had high expression of HER2, and gene amplification was confirmed in <br/>assessable cases. In I-type tumours, high expression of HER3 was a favourable prognostic factor, but not <br/>independent of other prognostic factors. <br/>Several of the potentially treatment predictive associations described in this thesis are novel, and may be of <br/>clinical interest if the results can be repeated in other cohorts and if the mechanistic basis is understood. The <br/>results presented here must be however be interpreted with caution, since the cohort is retrospective and many <br/>tests have been made.},
  author       = {Elebro, Jacob},
  isbn         = {978-91-7619-274-0},
  keyword      = {Periampullary adenocarcinoma,Pancreatic cancer,bile duct cancer,ampullary adenocarcinoma,duodenal adenocarcinoma,Immunohistochemestry,prognosis},
  language     = {eng},
  pages        = {83},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  title        = {Prognostic factors in periampullary adenocarcinoma. A retrospective study over an 11 year period.},
  year         = {2016},
}