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- Andersson, G., et al.
(författare)
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Stromal progesterone receptor expression and long-term survival in patients with resected periampullary adenocarcinoma
- 2018
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 29:Suppl. 8, s. 262-263
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Early trials have reported a beneficial effect from tamoxifen treatment in patients with unresectable pancreatic cancer, in particular in women. However, the presence and prognostic significance of female hormone receptors in pancreatic or other periampullary cancers has not yet been described. Methods: Immunohistochemical screening of normal and malignant pancreatic tissue revealed that the predominantly expressed female hormone receptor was the progesterone receptor (PgR), in particular in the cancer-associated stroma. The impact of PgR expression on overall survival (OS) was further examined on tissue microarrays with primary tumours from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinoma. Results: Median follow-up time was 29.7 (range 1.9–185.1) months. Stromal PgR positivity (PgR+), allover denoted in 31% of the cases, was significantly higher in pancreatobiliary-type than in intestinal-type tumours (38.7% vs 19.0%, p = 0.008), with an equal distribution between sexes. Stromal PgR+ was significantly associated with a prolonged OS in KRAS-mutated tumours, whereas the opposite was seen in KRAS wild-type tumours (p for interaction =0.015). This association was particularly evident in women, with a median OS of 60.5 months for PgR+/KRAS mutated tumours and 9.9 months for PgR+/KRAS wild-type tumours (p for interaction <0.001). PgR expression was not prognostic in male patients. Conclusions: The finding of stromal PgR expression, and its link to clinical outcome in a considerable proportion of pancreatic and other periampullary cancers is novel. The concept of tamoxifen treatment for patients with unresectable disease, in particular elderly women, should be pursued, and PgR and KRAS may be relevant biomarkers for improved patient stratification.
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| 2. |
- Lundgren, S., et al.
(författare)
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Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma
- 2018
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 29:Suppl. 8, s. 463-463
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: There is a great unmet clinical need to identify patients with thin primary cutaneous melanomas (T1, Breslow thickness ≤ 1 mm) who have a high risk for tumor recurrence and death from melanoma. Kin of IRRE-like protein 1 (KIRREL/NEPH1) is expressed in podocytes and involved in glomerular filtration, but its expression in human cancer has not yet been reported. Screening in the Human Protein Atlas portal revealed a particularly high expression of KIRREL in melanoma, both at the mRNA and protein levels. In this study, we followed up on these findings and examined the prognostic value of KIRREL in a population-based cohort of melanoma. Methods: Immunohistochemical analysis of KIRREL was performed on tissue microarrays with a subset of primary tumors and paired lymph node metastases from an original cohort of 268 incident cases of melanoma in the Malmö Diet and Cancer study. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the relationship between KIRREL expression and time to recurrence (TTR) and melanoma-specific survival (MSS). The prognostic value of KIRREL mRNA expression was examined in 102 melanoma cases in The Cancer Genome Atlas (TCGA). Results: Membranous/cytoplasmic expression of KIRREL was detected in 158/185 (85.4%) primary tumours and 18/19 (94.7%) metastases, in various fractions and intensities. High expression of KIRREL was significantly associated with several unfavourable clinicopathological factors. KIRREL expression was not prognostic in tumours >1 mm thickness, but in T1 tumours (n = 106, median thickness 0.58, range 0.08-1.00), high expression of KIRREL was significantly associated with a reduced TTR, independent of and outperforming absolute thickness in mm and ulceration (HR = 4.54, 95% CI 1.01-20.45), and borderline significantly associated with MSS. High mRNA levels of KIRREL were associated with a significantly reduced overall survival in the TCGA (p = 0.028). Conclusions: KIRREL is not only a novel potential diagnostic marker for melanoma, but may also be a useful prognostic biomarker for improved stratification of patients with thin melanoma. These findings may be of high clinical relevance and therefore merit further validation.
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