Kliniczne znaczenie rozpoznania zmiany pęcherzykowej bliżej nieokreślonej (grupa III wg Systemu Bethesda) w biopsji aspiracyjnej cienkoigłowej (BAC)

  Introduction: Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). Material and methods: Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. Results: From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of “Papillary Thyroid Carcinoma” and one “Suspicious for Papillary Thyroid Carcinoma”. From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was “Suspicious for Malignancy”. In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. Conclusions: The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment. (Endokrynol Pol 2016; 67 (1): 12–16)    Wstęp: Zmiana pęcherzykowa bliżej nieokreślona (grupa III) należy do najbardziej kontrowersyjnej kategorii systemu Bethesda. Brak jest polskich opracowań określających stopień ryzyka wystąpienia nowotworu złośliwego po rozpoznaniu zmiany z grupy III. Celem pracy było określenie ryzyka złośliwości po rozpoznaniu zmiany pęcherzykowej bliżej nieokreślonej w materiale Centrum Onkologii w Gliwicach. Materiał i metody: Analizie poddano 395 rozpoznań z grupy III BAC tarczycy wykonanych w latach 2010–2015. Oceniono zgodność pierwotnego rozpoznania grupy III z rozpoznaniami z kolejnych BAC i wynikami badań histopatologicznych. Wyniki: Na 395 rozpoznań grupy III zoperowano ze wskazań klinicznych 27 pacjentów i rozpoznano 6 raków. Ponowną BAC wykonano w 180 przypadkach i pierwotne rozpoznanie potwierdzono w 41 przypadkach. Po drugiej BAC 2-krotnie rozpoznano raka brodawkowatego lub jego podejrzenie. U 8 operowanych w tej serii potwierdzono wcześniejsze cytologiczne rozpoznanie raka u 2. Trzecią i kolejne BAC wykonano u 46 pacjentów i w jednym przypadku podejrzewano raka. Ryzyko raka w zmianie pęcherzykowej bliżej nieokreślonej w analizowanym materiale wynosi 2,78%. Uwzględniając wszystkie powtórnie wykonane 56 BAC, w których potwierdzono pierwotne rozpoznanie grupy III, ryzyko maleje do 2,43%. Wnioski: Rozpoznanie zmiany pęcherzykowej bliżej nieokreślonej przy braku wskazań klinicznych nie jest podstawą do wszczęcia postępowania chirurgicznego. (Endokrynol Pol 2016; 67 (1): 12–16)

Podejrzenie nowotworu pęcherzykowego czy nowotwór pęcherzykowy? Dylemat patologa i chirurga

  Introduction: Cytological material obtained from Fine Needle Aspiration Biopsy (FNAB) does not permit us to distinguish between follicular carcinomas, adenomas, and hyperplastic nodules. The limitations of the method are: lack of possibility to assess the presence of tumour capsule, eventual capsular invasion, and angioinvasion. An unequivocal conclusion of whether what we have to deal with is a neoplastic or benign lesion is possible only after histopathological examination. The aim of the study was to confirm justification for using the term “Suspicious for Follicular Neoplasm” (SFN) in cytological diagnostics of thyroid carcinoma. Material and methods: Three hundred and fifty-two primary SFN FNAB diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) obtained from 2010 to 2015 in the Institute of Oncology in Gliwice were analysed, and their correlation with histopathological diagnoses was verified. Results: In the Institute of Oncology in Gliwice, 352 primary SFN diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) were established. Surgical treatment was undertaken after first FNAB in six cases, giving confirmation of a neoplasm in five cases, one of which was a follicular carcinoma. Second FNAB performed in 90 patients confirmed DC IV diagnosis in 53 cases. Third FNAB concerned 26 patients, providing another 14 diagnoses of DC IV. 26 out of 352 patients were subjected to surgery, and then histopathological examination confirmed a neoplasm in 19 cases (which comprises 73%), five of which were carcinomas. Conclusions: High positive predictive value PPV = 73% of SFN diagnosis justifies undertaking surgical treatment in any case of this diagnosis. (Endokrynol Pol 2016; 67 (1): 17–22)    Wstęp: Materiał cytologiczny biopsji aspiracyjnej cienkoigłowej (BAC) tarczycy nie pozwala na zróżnicowanie raków pęcherzykowych, gruczolaków i guzków rozrostowych. Ograniczeniem metody jest brak możliwości określenia obecności torebki guza, jej ewentualnego nacieku oraz angioinwazji. Jednoznaczne rozstrzygnięcie czy mamy do czynienia ze zmianą nowotworową czy łagodną jest możliwe dopiero po badaniu histopatologicznym. Celem pracy było uzasadnienie celowości używania terminu „podejrzenie nowotworu pęcherzykowego” w diagnostyce cytologicznej raka tarczycy. Materiał i metody: Poddano analizie 352 wyniki BAC tarczycy wykonanych w Instytucie Onkologii (IO) w Gliwicach w latach 2010–2015 i ich korelację z rozpoznaniem histopatologicznym. Wyniki: W IO rozpoznanie podejrzenie nowotworu pęcherzykowego (grupa IV wg Systemu Bethesda) postawiono pierwotnie w 352 przypadkach. Leczenie operacyjne podjęto po pierwszej BAC w 6 przypadkach uzyskując potwierdzenie nowotworu w 5 przypadkach w tym jednego raka pęcherzykowego. Powtórna BAC przeprowadzona u 90 pacjentów potwierdziła rozpoznanie grupy IV w 53 przypadkach. Trzecią BAC przeprowadzono u 26 chorych, uzyskując kolejnych 14 rozpoznań grupy IV. Leczeniu operacyjnemu poddano 26 pacjentów na 352 rozpoznania nowotworu pęcherzykowego, uzyskując potwierdzenie nowotworu w 19 przypadkach, co stanowi 73% w tym raka 5 razy. Wnioski: Wysoka dodatnia wartość predykcyjna PPV = 73% rozpoznania „podejrzenie nowotworu pęcherzykowego” uzasadnia podjęcie leczenia operacyjnego w każdym przypadku tego rozpoznania. (Endokrynol Pol 2016; 67 (1): 17–22)

Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan–Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan–Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian–epithelial origin of the tumor

Image_4_Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy.pdf

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.</p

Image_8_Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy.pdf

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.</p

Table_2_Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy.xlsx

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.</p

Image_1_Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy.pdf

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.</p

Image_6_Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy.pdf

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.</p

Table_5_Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy.xlsx

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.</p