The Concept of Stroma AReactive Invasion Front Areas (SARIFA) as a new prognostic biomarker for lipid-driven cancers holds true in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a 'difficult-to-treat' entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion front areas), which are areas at the tumour invasion front lacking desmoplastic stroma reaction upon malignant invasion in the surrounding tissue, leading to direct contact between tumour cells and adipocytes. SARIFA showed its significance in gastric and colorectal carcinoma, revealing lipid metabolism alternations that promote tumour progression. METHODS: We reviewed the SARIFA status of 166 PDAC cases on all available H&E-stained tumour slides from archival Whipple-resection specimens. SARIFA positivity was defined as SARIFA detection in at least 66% of the available slides. To investigate alterations in tumour metabolism and microenvironment, we performed immunohistochemical staining for FABP4, CD36 and CD68. To verify and quantify a supposed delipidation of adipocytes, adipose tissue was digitally morphometrised. RESULTS: In total, 53 cases (32%) were classified as SARIFA positive and 113 (68%) as SARIFA negative. Patients with SARIFA-positive PDAC showed a significantly worse overall survival compared with SARIFA-negative cases (median overall survival: 11.0 months vs. 22.0 months, HR: 1.570 (1.082-2.278), 95% CI, p = 0.018), which was independent from other prognostic markers (p = 0.014). At the invasion front of SARIFA-positive PDAC, we observed significantly higher expression of FABP4 (p < 0.0001) and higher concentrations of CD68+ macrophages (p = 0.031) related to a higher risk of tumour progression. CD36 staining showed no significant expression differences. The adipocyte areas at the invasion front were significantly smaller, with mean values of 4021 ± 1058 µm2 and 1812 ± 1008 µm2 for the SARIFA-negative and -positive cases, respectively (p < 0.001). CONCLUSIONS: SARIFA is a promising prognostic biomarker for PDAC. Its assessment is characterised by simplicity and low effort. The mechanisms behind SARIFA suggest a tumour-promoting increased lipid metabolism and altered immune background, both showing new therapeutic avenues.

Stroma AReactive Invasion Front Areas (SARIFA) - a new prognostic biomarker in gastric cancer related to tumor-promoting adipocytes.

Compared to other malignancies, there is a lack of easy-to-evaluate biomarkers for gastric cancer, which is associated with an adverse clinical outcome in many cases. Here, we present Stroma AReactive Invasion Front Areas (SARIFA) as a new histological prognostic marker. We defined SARIFA as the direct contact between a cluster of tumor glands/cells comprising at least five tumor cells and inconspicuous surrounding adipose tissue at the invasion front. A total of 480 adenocarcinomas of the stomach and the gastroesophageal junction from two different collections were classified according to SARIFA. To understand the potential underlying mechanisms, a transcriptome analysis was conducted using digital spatial profiling (DSP). It was found that 20% of the tumors were SARIFA-positive. Kappa values between the three pathologists were good in both collections: 0.74 and 0.78. Patients who presented SARIFA-positive tumors had a significantly lower overall survival in Collections A (median: 20.0 versus 44.0 months; p = 0.014, n = 160) and B (median: 15.0 versus 41.0 months; p < 0.0001, n = 320). SARIFA positivity emerged as a negative independent prognostic factor for overall survival (HR 1.638, 95% CI 1.153-2.326, p = 0.006). Using DSP, the most upregulated genes in SARIFA-positive cases were those associated with triglyceride catabolism and endogenous sterols. COL15A1, FABP2, and FABP4 were differentially expressed in positive cases. At the protein level, the expression of proteins related to lipid metabolism was confirmed. SARIFA combines low inter-observer variability, minimal effort, and high prognostic relevance, and is therefore an extremely promising biomarker related to tumor-promoting adipocytes in gastric cancer. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Impact of uPA/PAI-1 and disseminated cytokeratin-positive cells in breast cancer.

BACKGROUND: The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects. METHODS: We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18. RESULTS: DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without chemotherapy, the prognostic impact of uPA and PAI-1 was enhanced in cases with additional dCK-positivity (triple +). In cases without chemotherapy, triple-positive status was independently prognostic (HR: 9.3 CI: 1.1-75) next to T stage. CONCLUSIONS: uPA and PAI-1 seem to influence the metastatic potential of dCK+ cells, which underlines its important role in tumor progression.

Malignancies associated with GIST: a retrospective study with molecular analysis of KIT and PDGFRA.

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common soft tissue tumors of the GI tract. Studies have been published reporting additional neoplasms in GIST patients. This study aimed to evaluate possible associations of mutation type, morphology, and clinical aspects of GISTs. METHODS: All cases of GIST were identified from our pathology files. Coding exons of KIT and PDGFRA in GISTs with additional malignancies were sequenced. RESULTS: A total of 70 of 188 (37%) retrieved patients with confirmed diagnosis of GIST showed at least one additional malignant neoplasm. Fifty of these GISTs were located in the stomach (71%), 8 in the small intestine (11%), 5 in the colon/rectum (7%), and 7 cases (6.2%) were of undetermined sites of origin. The distribution of identified mutations was similar to that described in GISTs without secondary malignancies. A total of 37 of 57 cases (65%) showed mutations in the KIT gene exon 11, 3 (5%) cases in exon 9, and 1 (2%) case in exon 13. Nine tumors (16%) had mutations of the PDGFRA gene. KIT and PDGFRA wild-type status were found in seven cases (12%). Most of the secondary neoplasms were located within the GI tract (34%), in the urogenital system (24%), or the breast/female genital tract (20%). CONCLUSION: This study confirms the high rate of additional malignant tumors in GIST patients. GIST features in these cases are very similar to those with sole GIST.

EndoPredict versus uPA/PAI-1 in breast cancer: Comparison of markers and association with clinicopathological parameters.

We retrospectively investigated concordance of EndoPredict (EPclin) with urokinase plasminogen activator and plasminogen activator inhibitor-1 (uPA/PAI-1) in 72 breast cancer patients and compared the results with grading, molecular subtype and chemotherapy recommendation. Compared to uPA/PAI-1, EPclin proved to be more conservative concerning correlation with clinicopathological parameters and was significantly associated with the recommendation of adjuvant chemotherapy.

Level of interobserver variability estimation as a valuable tool: assessment of tumour budding in colon cancer.

AIMS: Tumour budding is considered to be a good marker for progression and prognosis in colorectal carcinomas. A uniform classification system has been established recently. The natural element of uncertainty in the practice of human medicine is also exhibited in the assessment of tumour budding. We tested the hypothesis that interobserver variability can be estimated during the assessment process and investigated its potential clinical implication. METHODS AND RESULTS: Six investigators with different levels of experience could perceive different levels of difficulty (LOD) and estimated different levels of interobserver variability (LOIV) (Li1, lower than average; Li2, average; Li3, higher than average) during the assessment of tumour budding in 244 cases of colon cancer (pT3/4). In total, the LOIV showed following distribution: Li1: 36.1%, Li2: 43.9% and Li3: 20.0%. The LOIV was correlated significantly with the LOD given by the investigator. In total, the agreement rates with the final consensus classification were: Li1: 93.4%, Li2: 78.5% and Li3: 58.4%. The relative risk of disagreement with the final consensus classification was more than six times higher when a case was estimated to have a high rather than a low interobserver variability. CONCLUSION: Our data show that the investigator can estimate the interobserver variability during the ongoing rating process in pT3/4 colon cancer. The LOIV/LOD seems to be a valuable parameter of the assessment quality. For Li3 cases further measures seem mandatory.

Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011.

BACKGROUND: Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. METHODS: Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. RESULTS: The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97-0.97), sex (OR 1.18, 95% CI 1.11-1.25), date of diagnosis (OR 1.05, 95% CI 1.04-1.06), 'diagnosis during screening' (OR 3.24, 95% CI 2.50-4.19) and place of residence (OR 1.23, 95% CI 1.16-1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8-83.9%). CONCLUSIONS: No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.

Clinical Significance of International Union Against Cancer pN Staging and Lymph Node Ratio in Node-Positive Colorectal Cancer after Advanced Lymph Node Dissection.

BACKGROUND: Lymph node retrieval in colorectal cancer can be improved by using advanced histopathological techniques like methylene blue-assisted lymph node dissection, which results in a doubling or even tripling of the lymph node count in comparison with conventional lymph node dissection techniques. However, it is not clear whether the established lymph node staging systems are suitable for predicting patients' prognoses under these circumstances. OBJECTIVE: The aim of this study was to determine whether the current lymph node staging systems are suitable when advanced dissection methods are used. DESIGN: This is a retrospective cohort study. SETTING AND PATIENTS: We formed a study group (methylene blue-assisted lymph node dissection) of 293 patients and a control group (conventional lymph node dissection) of 232 patients, each with node-positive cases. Conventional pN staging according to the International Union Against Cancer, seventh edition, and lymph node ratio were applied. MAIN OUTCOME MEASURES: Overall survival was compared by using the different staging systems in a uni- and multivariable fashion. RESULTS: The lymph node ratio values were reduced in the advanced methylene blue-assisted lymph node dissection group in comparison with the conventional lymph node dissection group (0.1 vs 0.3, p < 0.001). Although pN staging proved to be reliable, the cutoff values for lymph node ratio staging had to be adapted. The new cutoffs (0.07, 0.15, and 0.34) were prognostic. However, multivariable analysis revealed pN staging and vascular invasion, but not lymph node ratio, as independently prognostic in the methylene blue-assisted lymph node dissection group. LIMITATIONS: The study group and historical control group are not perfectly balanced because the case number in the stage III subgroup of the control group is small. CONCLUSIONS: pN staging proved to be a robust prognostic marker in colorectal cancer under the circumstances of improved lymph node harvest. After adaptation of the cutoff values, lymph node ratio is also prognostic but not superior to pN staging.

Lymph node hypoplasia is associated with adverse outcomes in node-negative colon cancer using advanced lymph node dissection methods.

PURPOSE: Lymph node size as a prognostic parameter has not been investigated well in the past. Recent data, however, have indicated that this parameter could be even more important than the lymph node count. METHODS: Based on the results of earlier studies, we analyzed the lymph node size and number of node-negative colon cancer patients with regard to survival. Data from 115 node-negative cases of colon cancer were analyzed. Lymph nodes with diameters ≤5 mm were defined as small, and all other lymph nodes were classified as intermediate/large in size and labeled LN5. All of the cases were categorized according to the number of LN5s. The LN5 very low (LN5vl) group included cases with less than two LN5s. All of the other cases were assigned to the LN5 low/high (LN5l/h) group. RESULTS: The overall survival analysis revealed significantly worse outcomes for the LN5vl group, with a mean survival of 34 months compared to the LN5l/h group, with a mean survival of 40 months (P = 0.022). After adjusting for the pT1/2 and pT3/4 stages, we still found a significant outcome difference (P = 0.012). Multivariate analysis identified LN5vl and T-stage as being independently correlated with the outcome. The vast majority of LN5vl cases (91 %) were located in the left colon. The location itself, however, was not prognostic (P = 0.478). CONCLUSION: LN5 count, as a marker of immune response, could be shown as being prognostic in node-negative colon cancer. Patients with low LN5 counts showed poor outcomes. These patients could perhaps profit from adjuvant chemotherapy.

The WERA cancer center matrix: Strategic management of patient access to precision oncology in a large and mostly rural area of Germany.

PURPOSE: Providing patient access to precision oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center. METHODS: As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA´s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2243). As second dimension, we added the provenance of patients receiving general cancer care by WERA. Clustering our catchment area along these two dimensions set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria. RESULTS: The WERA matrix overlooked an active screening area of 821 postal code areas - representing about 50 % of Bavaria´s spatial expansion and more than six million inhabitants. The WERA matrix identified regions successfully connected to our outreach structures in terms of subsidiarity - with general cancer care mainly performed locally but PO performed in collaboration with WERA. We also detected postal code areas with a potential PO backlog - characterized by high levels of cancer care performed by WERA and low levels or no MTB representation. CONCLUSIONS: The WERA matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers.

Methylene blue-assisted lymph node dissection technique is not associated with an increased detection of lymph node metastases in colorectal cancer.

Lymph node staging is of paramount importance for prognosis estimation and therapy stratification in colorectal cancer. A high number of harvested lymph nodes is associated with an improved outcome. Methylene blue-assisted lymph node dissection effectively improves the lymph node harvest and ensures sufficient staging. Now, the effect on node positivity rate and stage-related outcome was investigated. The study cohort with advanced lymph node dissection consisted of 669 colorectal cancer cases of all stages, which were collected between 2007 and 2012. A historical collection of 663 cases investigated with conventional techniques between 2002 and 2004 served as control. Lymph node harvest was dramatically improved in the study group with mean lymph node numbers of 34 ± 17 vs 13 ± 5 (P<0.001) and sufficient staging rates of 98% vs 62% (P<0.001). However, neither the rate of nodal positive cases (37% vs 37%; P = 0.98) nor the rate of N2 cases differed between the two groups (14% vs 13%; P = 0.80). Furthermore, no differences were found concerning the outcome in both groups. The advanced lymph node dissection technique guarantees adequate histopathological lymph node staging in virtually all cases of colorectal cancer and is therefore extremely helpful. The hypothesis that it also provides a higher sensitivity in detecting metastases, however, could be not proved.

The clinical significance of lymph node size in colon cancer.

To date, the clinical value of lymph node size in colon cancer has been investigated only in a few studies. Only in radiological diagnosis is lymph node size routinely recognized, and nodes ≥10 mm in diameter are considered pathologic. However, the few studies regarding this topic suggest that lymph node size is not a reliable indicator of metastatic disease. Moreover, we hypothesized that increasing lymph node size is associated with favorable outcome. By performing a morphometric study, we investigated the clinical significance of lymph node size in colon cancer in terms of metastatic disease and prognosis. A cohort of 237 cases with excellent lymph node harvest (mean lymph node count: 33±17) was used. The size distribution in node-positive and -negative cases was almost identical. In all, 151 out of the 305 metastases detected (49.5%) were found in lymph nodes with diameters ≤5 mm. Only 25% of lymph nodes >10 mm showed metastases. Minute lymph nodes ≤1 mm were involved only very rarely (2 of 81 cases). In 67% of the cases, the largest positive lymph node was <10 mm. The prognostic relevance of lymph node size was investigated in a subset of 115 stage I/II cases. The occurrence of ≥7 lymph nodes that were >5 mm in diameter was significantly associated with better overall survival. Our data show that lymph node size is not a suitable factor for preoperative lymph node staging. Minute lymph nodes have virtually no role in correct histopathological lymph node staging. Finally, large lymph nodes in stage I/II disease might indicate a favorable outcome.

ALK, NUT, and TRK Do Not Play Relevant Roles in Gastric Cancer-Results of an Immunohistochemical Study in a Large Series.

ALK, NUT, and TRK are rare molecular aberrations that are pathognomonic for specific rare tumors. In low frequencies, however, they are found in a wide range of other tumor entities. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of the immunohistochemical expressions of ALK, NUT, and TRK in 477 adenocarcinomas of the stomach and gastroesophageal junction. Seven cases (1.5%) showed an expression of TRK. In NGS, no NTRK fusion was confirmed. No case with ALK or NUT expression was detected. ALK, NUT, and NTRK expression does not seem to play an important role in gastric carcinomas.

Semiautomatic analysis of tumor proportion in colon cancer: Lessons from a validation study.

The tumor stroma ratio (TSR) is a promising histopathologic prognostic biomarker, which could allow for more accurate risk stratification and improved patient management in colorectal cancer. The purpose of our research was to validate the results of a previous study, which had suggested that not only a low but also a high tumor proportion (TP) might be an independent risk factor for occurrence of distant metastasis and worse overall survival using a semiautomatic image analysis approach with the open-source software ImageJ. We investigated 253 pT3 and pT4 adenocarcinomas of no special type. The previously established thresholds (PES-cut-offs) used to classify the patients (previous 3-tiered-classification) according to the tumor proportion (TP) in a highTP (TP ≥ 54%), a mediumTP (TP < 54% ∩ TP >15%) and a lowTP (TP ≤ 15%) group did not show a significant risk stratification. Even the adjustment of these threshold revealed no significant results. Therefore, a receiver-operating characteristic (ROC) analysis was performed to establish the cut-off with the most significant predictive power and a "new 2-tiered-classification" using this cut-off (40% at MinTP) showed a significantly shorter absence of metastasis for patients with a low TP (p = 0.007). These results confirm that a low TP is associated with an adverse prognosis. This study did not confirm the previous assumption that a high TP might also be a risk factor for occurrence of metastasis. Furthermore, it demonstrates that this semiautomatic technique is not superior to the established method, so that approaches to enhance prognostic techniques should continue.

Ultrastaging Using Ex Vivo Sentinel Lymph Node Mapping and One-Step Nucleic Acid Amplification (OSNA) in Gastric Cancer: Experiences of a European Center.

BACKGROUND: In this study, the effectiveness of One-step nucleic acid amplification (OSNA) in combination with ex vivo SLN mapping is compared with conventional histology including immunohistochemistry. METHODS: LNs were retrieved from gastrectomy specimens in an unfixed state. After ex vivo SLN mapping using methylene-blue, LNs were sliced to provide samples for histology and OSNA. RESULTS: In total, 334 LNs were retrieved in the fresh state from 41 patients. SLN detection was intended in 40 cases but was successful in only 29, with a correct LN status prediction in 23 cases (79%). Excluding one case out of 41 with a failure likely caused by a processing error, OSNA showed a high effectiveness with sensitivity, specificity, and accuracy rates of 85.4%, 93.5%, and 92.4%, respectively. The LN status could be predicted in all but one case, in which the single positive LN was not eligible for OSNA testing. Moreover, OSNA evaluation led to upstaging from N0 to N+ in three cases (14%). CONCLUSION: The ex vivo SLN protocol used resulted in a relatively poor detection rate. However, the OSNA method was not hampered by this detection rate and proved its potential to increase the sensitivity of metastases detection.

Associations between Weather, Air Quality and Moderate Extreme Cancer-Related Mortality Events in Augsburg, Southern Germany.

While many authors have described the adverse health effects of poor air quality and meteorological extremes, there remain inconsistencies on a regional scale as well as uncertainty about the single and joint effects of atmospheric predictors. In this context, we investigated the short-term impacts of weather and air quality on moderate extreme cancer-related mortality events for the urban area of Augsburg, Southern Germany, during the period 2000-2017. First, single effects were uncovered by applying a case-crossover routine. The overall impact was assessed by performing a Mann-Whitney U testing scheme. We then compared the results of this procedure to extreme noncancer-related mortality events. In a second step, we found periods with contemporaneous significant predictors and carried out an in-depth analysis of these joint-effect periods. We were interested in the atmospheric processes leading to the emergence of significant conditions. Hence, we applied the Principal Component Analysis to large-scale synoptic conditions during these periods. The results demonstrate a strong linkage between high-mortality events in cancer patients and significantly above-average levels of nitrogen dioxide (NO2) and particulate matter (PM2.5) during the late winter through spring period. These were mainly linked to northerly to easterly weak airflow under stable, high-pressure conditions. Especially in winter and spring, this can result in low temperatures and a ground-level increase and the accumulation of air pollution from heating and traffic as well as eastern lateral advection of polluted air. Additionally, above-average temperatures were shown to occur on the days before mortality events from mid-summer through fall, which was also caused by high-pressure conditions with weak wind flow and intense solar radiation. Our approach can be used to analyse medical data with epidemiological as well as climatological methods while providing a more vivid representation of the underlying atmospheric processes.

Comprehensive Immunohistochemical Study of the SWI/SNF Complex Expression Status in Gastric Cancer Reveals an Adverse Prognosis of SWI/SNF Deficiency in Genomically Stable Gastric Carcinomas.

The SWI/SNF complex has important functions in the mobilization of nucleosomes and consequently influences gene expression. Numerous studies have demonstrated that mutations or deficiency of one or more subunits can have an oncogenic effect and influence the development, progression, and eventual therapy resistance of tumor diseases. Genes encoding subunits of the SWI/SNF complex are mutated in approximately 20% of all human tumors. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of immunohistochemical expression of proteins of the SWI/SNF complexes, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. Complete loss of SMARCA4 was detected in three cases (0.6%) and was associated with adverse clinical characteristics. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.

A Retrospective 5-Year Single Center Study Highlighting the Risk of Cancer Predisposition in Adolescents and Young Adults.

The knowledge of inherited cancer susceptibility opens a new field of cancer medicine. We conducted a retrospective single-center cohort study. Data of AYA cancer patients registered between January 2014 and December 2018 were analyzed. The median age at cancer diagnosis of 704 patients (343 males, 361 females) was 32 years (range, 15-39 years), median follow-up was 181 days (range, 1-1975 days). Solid tumors were diagnosed in 575 (81.7%) patients, hematologic malignancies in 129 (18.3%) patients. Multiple primary cancers were reported in 36 (5.1%) patients. Malignancies that may be indicators of inherited cancer susceptibility were diagnosed in 2.6% of patients with cancers of the endocrine system, in 73% of cancers of the gastrointestinal system, in 88% of tumors of the central nervous system, in 92% of cancers of the urinary tract, and in 59% of head and neck tumors. In addition, all patients with breast cancer, sarcoma, and peripheral nerve sheath tumor were in need of genetic counselling. In sum, at least 181 of 704 (25.7%) AYA cancer patients presented with malignancies suspicious of harboring pathogenic germline variants. Evaluation of AYA cancer patients for hereditary cancer predisposition needs to be integrated into daily practice.

A Mass Spectrometry Imaging Based Approach for Prognosis Prediction in UICC Stage I/II Colon Cancer.

Currently, pathological evaluation of stage I/II colon cancer, following the Union Internationale Contre Le Cancer (UICC) guidelines, is insufficient to identify patients that would benefit from adjuvant treatment. In our study, we analyzed tissue samples from 276 patients with colon cancer utilizing mass spectrometry imaging. Two distinct approaches are herein presented for data processing and analysis. In one approach, four different machine learning algorithms were applied to predict the tendency to develop metastasis, which yielded accuracies over 90% for three of the models. In the other approach, 1007 m/z features were evaluated with regards to their prognostic capabilities, yielding two m/z features as promising prognostic markers. One feature was identified as a fragment from collagen (collagen 3A1), hinting that a higher collagen content within the tumor is associated with poorer outcomes. Identification of proteins that reflect changes in the tumor and its microenvironment could give a very much-needed prediction of a patient's prognosis, and subsequently assist in the choice of a more adequate treatment.

Stroma AReactive Invasion Front Areas (SARIFA)-A New Easily to Determine Biomarker in Colon Cancer-Results of a Retrospective Study.

Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor-stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p < 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (<1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers.