15 research outputs found
Hypopharyngeal carcinoma in Finland from 2005 to 2014 : outcome remains poor after major changes in treatment
Purpose Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. Methods We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. Results The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. Conclusions The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.Peer reviewe
Hypopharyngeal carcinoma in Finland from 2005 to 2014: outcome remains poor after major changes in treatment
Purpose Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. Methods We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. Results The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. Conclusions The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.</p
Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression
<p>Abstract</p> <p>Background</p> <p>Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, <it>TWIST </it>and <it>SNAI1</it>, are fundamental in regulating EMT.</p> <p>Methods</p> <p>Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas.</p> <p>Results</p> <p>Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively).</p> <p>Conclusion</p> <p>TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.</p
SIP1 predicts progression and poor prognosis in pharyngeal squamous cell carcinoma
Objectives: The epithelial-mesenchymal
transition (EMT) is a crucial process in tumorigenesis
that enables tumor cells to invade and metastasize. The
transcription factors SIP1, SLUG, ZEB1, SNAI1, and
TWIST are fundamental in regulating EMT. We
investigated the relationships between several
clinicopathological variables, prognosis, and SIP1,
SLUG, or ZEB1 in a retrospective pharyngeal squamous
cell carcinoma (PSCC) cohort.
Study Design: Immunohistochemistry was used to
evaluate the expression of SIP1, SLUG, and ZEB1 in
108 tumor samples from a retrospective cohort of
patients with PSCC.
Results: Tumors with positive epithelial SIP1
immunostaining were more advanced (SIII-IV, p=0.02)
and had more lymph node metastases (p=0.04) than
SIP1-negative tumors. Tumors with positive stromal
staining of SIP1 relapsed more often than SIP1-negative
tumors (p=0.007). Negative SIP1 immunoreactivity
correlated significantly with better disease-specific
survival (DSS) and better overall survival (OS) (p=0.012
and p=0.003 for epithelial reactivity, p=0.018 and
p=0.003 for stromal reactivity, respectively). Lack of
epithelial SIP1 expression remained an independent and
favorable prognostic factor in a Cox proportional
hazards model (p=0.046), together with high Karnofsky
performance status score and low T class (p<0.001 for
both). Co-expression of SNAI1, TWIST, and SIP1 in
tumor epithelium predicted even shorter DSS than SIP1
expression alone (p<0.001) in the present study cohort.
Conclusions: SIP1 is related to cancer progression and
appears to be an independent prognostic factor in PSCC
Hypopharyngeal carcinoma in Finland from 2005 to 2014 : outcome remains poor after major changes in treatment
Purpose Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. Methods We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. Results The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. Conclusions The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.Peer reviewe
Transcription factor snail1 expression and poor survival in pharyngeal squamous cell carcinoma
Snail1, a key regulator of epithelialmesenchymal
transition (EMT), plays an important role
in tumour progression. Previous studies of snail1 have
mainly focused on the epithelial tumour cells. The
objective of this study was to evaluate the expression of
snail1 protein in endothelial cells, stromal
myofibroblasts and malignant epithelial cells of
pharyngeal squamous cell carcinomas (PSCC), as well
as its relation to clinicopathological features and
survival. One hundred and ten tissue microarray samples
were analyzed for snail1 expression using
immunohistochemistry. In endothelial cells snail1
expression was observed in 51 (48%) of 107 cases and it
predicted reduced disease specific survival (DSS)
(p=0.009). In 49 (46%) tumour samples snail1 immunostaining
was detected in stromal myofibroblasts and
there was a tendency to poorer DSS in that group
(p=0.067). Snail1 expression in endothelial cells and
stromal myofibroblasts is also associated with
hypopharyngeal tumours (p=0.01 and p=0.038
respectively), increasing T category (T3-4) (p=0.005,
p=0.037 respectively) and poorer general condition of
the patient (Karnofsky performance status score <70;
p=0.029, p=0.039 respectively). Moreover endothelial
expression correlated with advanced stage (III-IV)
(p=0.005) and poorer differentiation (grade 2-3;
p=0.012). In malignant epithelial cells snail1
immunostaining was detected in 75 of 110 cases (68%).
Expression of the protein was more common in
hypopharyngeal tumours (p=0.044). Snail1 positive tumours associated with a lower Karnofsky performance
status score (p=0.039) and regional failure (p=0.042).
Our findings indicate that snail1 protein expression in
endothelial cells and to some extent also in tumour
stromal myofibroblasts seems to be a predictor of poor
survival in PSCC. The presence of snail1 protein in
tumour microenvironment rather than in malignant
epithelial tumour cells may induce tissue remodelling
and tumour progression
Atypical PKCs activate Vimentin to facilitate prostate cancer cell motility and invasion
Epithelial-to-mesenchymal transition transcription factors in cancer-associated fibroblasts
Beyond inducing epithelial-to-mesenchymal transcription (EMT), transcriptional factors of the Snail, ZEB and Twist families (EMT-TFs) control global plasticity programmes affecting cell stemness and fate. Literature addressing the reactivation of these factors in adult tumour cells is very extensive, as they enable cancer cell plasticity and fuel both tumour initiation and metastatic spread. Incipient data reveal that EMT-TFs are also expressed in fibroblasts, providing these with additional properties. Here, I will review recent reports on the expression of EMT-TFs in cancer-associated fibroblasts (CAFs). The new model suggests that EMT-TFs can be envisioned as essential metastasis and chemoresistance-promoting molecules, thereby enabling coordinated plasticity programmes in parenchyma and stroma-tumour compartments
Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma
Copy number increase of oncoprotein CIP2A is associated with poor patient survival in human head and neck squamous cell carcinoma
BackgroundCIP2A, an inhibitor of PP2A tumour suppressor function, is a widely overexpressed biomarker of aggressive disease and poor therapy response in multiple human cancer types. MethodsCIP2A and DPPA4 copy number alterations and expression were analysed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in different cell lines and a tissue microarray of 52 HNSCC patients. Results were correlated with patient survival and other clinicopathological data. ResultsCIP2A and DPPA4 copy number increase occurred at a relatively high frequency in human HNSCC patient samples. CIP2A but not DPPA4 FISH status was significantly associated with patient survival. CIP2A detection by combining IHC with FISH yielded superior resolution in the prognostication of HNSCC. ConclusionsCIP2A copy number increase is associated with poor patient survival in human HNSCC. We suggest that the reliability and prognostic value of CIP2A detection can be improved by performing FISH analysis to CIP2A IHC positive tumours.Finnish Cancer Associations; Foundation of Finnish Cancer InstituteWe thank Dr. Ilpo Kinnunen for his kind assistance in preparing this manuscript. This work was supported by funding from Finnish Cancer Associations and from Foundation of Finnish Cancer Institute