IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.

BACKGROUND: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. METHODS: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. RESULTS: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs. 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. CONCLUSIONS: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

Effect of adjuvant chemotherapy on localized dedifferentiated low-grade osteosarcoma: a systematic review.

PURPOSE: Dedifferentiated low-grade osteosarcomas, which are considered high grade malignancies, can arise from the dedifferentiation of parosteal and low-grade osteosarcomas. Usually, localized dedifferentiated low-grade osteosarcomas are treated by wide resection, and the efficacy of adjuvant chemotherapy is controversial. We conducted a systematic review of studies that investigated the rates of mortality and significant events, such as recurrence and metastases, in localized dedifferentiated low-grade osteosarcoma patients who received wide resection only and in those who received wide resection and (neo-)adjuvant chemotherapy. METHODS: We identified 712 studies through systematic searches of Embase, PubMed, and the Cochrane Central Register of Controlled Trials databases. Of those studies, seven were included in this review and none were randomized controlled trials. In the seven studies, 114 localized dedifferentiated low-grade osteosarcoma patients were examined. RESULTS: Mortality rates of the resection plus chemotherapy (R + C) and the resection only (Ronly) groups were 20.3% and 11.4%, respectively [overall pooled odds ratio, 1.59 (P = 0.662); heterogeneity I2, 0%]. The local recurrence or distant metastasis rate in the R + C group was 36.7% and that in the Ronly group was 28.6% [overall pooled odds ratio, 1.37 (P = 0.484); heterogeneity I2 was 0%]. CONCLUSIONS: Results show a limited efficacy of adjuvant chemotherapy for localized dedifferentiated low-grade osteosarcoma. However, because this was a systematic review of retrospective studies that examined a small number of patients, future randomized controlled trials are needed.

An ultrasonography-cytology protocol for the diagnostic management of regional nodes in a subset of patients with Merkel cell carcinoma of the skin.

BACKGROUND: The status of regional lymph nodes (LNs) is one of the most consistent predictors of survival in Merkel cell carcinoma (MCC). In cases of clinically localized disease, current practice involves sentinel lymph node (SLN) assessment. OBJECTIVES: To propose ultrasonography (US) followed by fine needle aspiration cytology (FNAC) and immunohistochemistry as a useful diagnostic tool in the pre-surgical management of patients with MCC. METHODS: US of LNs was performed in 75 patients with MCC (22 with stage III tumours; 53 with stage I-II). In patients with US suspected disease, US coupled with FNAC of the LN was performed. Smears were examined by routine cytological staining supplemented with immunohistochemical staining for cytokeratin 20. All patients underwent surgical removal of regional LNs. RESULTS: In all 22 patients with stage III tumours, US was indicative of tumour deposits and FNAC confirmed metastases to LNs. In 11 of 53 patients with localized MCC without clinical evidence of nodal disease, US revealed enlarged, equivocal nodes where FNAC was performed. Ten LNs were cytologically positive for metastases, and one was negative. Upon histological examination, the FNAC-negative case showed a metastasis 5 mm in diameter. In all the other 42 cases with no clinical or US evidence of LN involvement, only SLN biopsy was performed and in six cases small metastatic foci were detected. Ultimately, of the 53 stage I-II MCC, 17 had positive LN involvement. In 10 cases (59%) metastases were detected by FNAC, and in seven cases, were detected by SLN biopsy. CONCLUSIONS: In a selected subset (∼20%) of patients with MCC with clinically localized disease, US followed by FNAC in the suspect LN is a valid alternative to the classical protocol of SLN histological examination.

Nanometrological porphyrins.

A new cationic silver N-alkylpyridylporphyrin complex is able to 'sense' nanometric conductive particles with a diameter below 10 nm. The luminescence of the molecule changes its maximum from red to blue when it embraces a conductive (metallic or semiconducting) nanoparticle. The change is explained on the basis of a charge transfer between the molecule and the conductive nanoparticle along with a geometrical distortion of the porphyric ring and pyridinium substituents. This new molecule could be used to sense nanoparticle contamination in the environment, in the industry of heterogeneous catalysis and many other branches of nanometrological applications.

Resonance Raman enhancement by the intralayer and interlayer electron-phonon processes in twisted bilayer graphene.

Twisted bilayer graphene is a fascinating system due to the possibility of tuning the electronic and optical properties by controlling the twisting angle [Formula: see text] between the layers. The coupling between the Dirac cones of the two graphene layers gives rise to van Hove singularities (vHs) in the density of electronic states, whose energies vary with [Formula: see text]. Raman spectroscopy is a fundamental tool to study twisted bilayer graphene (TBG) systems since the Raman response is hugely enhanced when the photons are in resonance with transition between vHs and new peaks appear in the Raman spectra due to phonons within the interior of the Brillouin zone of graphene that are activated by the Moiré superlattice. It was recently shown that these new peaks can be activated by the intralayer and the interlayer electron-phonon processes. In this work we study how each one of these processes enhances the intensities of the peaks coming from the acoustic and optical phonon branches of graphene. Resonance Raman measurements, performed in many different TBG samples with [Formula: see text] between [Formula: see text] and [Formula: see text] and using several different laser excitation energies in the near-infrared (NIR) and visible ranges (1.39-2.71 eV), reveal the distinct enhancement of the different phonons of graphene by the intralayer and interlayer processes. Experimental results are nicely explained by theoretical calculations of the double-resonance Raman intensity in graphene by imposing the momentum conservation rules for the intralayer and the interlayer electron-phonon resonant conditions in TBGs. Our results show that the resonant enhancement of the Raman response in all cases is affected by the quantum interference effect and the symmetry requirements of the double resonance Raman process in graphene.

Prognostic Impact of MCPyV and TIL Subtyping in Merkel Cell Carcinoma: Evidence from a Large European Cohort of 95 Patients.

Merkel cell carcinoma is a rare (∼ 2000 cases/year in the USA) but aggressive neuroendocrine neoplasm of the skin. In 2008, the Merkel cell polyomavirus (MCPyV) was found to be clonally integrated in approximately 80% of Merkel cell carcinomas. The remaining 20% have large numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens in virus-negative Merkel cell carcinoma and the Merkel cell polyomavirus oncogenes that are required for virus-positive tumor growth are highly immunogenic. Indeed, antigen-specific T cells detected in patients are frequently "dysfunctional/exhausted," and the inhibitory ligand PD-L1 is often expressed by Merkel cell carcinoma cells. These data led to point our attention on the quantity and the quality of the immune response in Merkel cell carcinoma. Here, we found CD8+ lymphocytes are the only singly evaluated lymphocyte subclass that strongly influenced overall survival and disease-specific survival in Merkel cell carcinoma. In addition, we highlighted as Merkel cell polyomavirus is a strong prognostic factor and as it prompts a host immune response involving various lymphocyte subclasses (CD3, CD8, FoxP3, and PD-L1 positive) in MCC. For this reason, we proposed a novel eye-based "immunoscore" model, obtained by tumor infiltrating lymphocytes subtyping (CD3, CD8, FoxP3, and PD-L1) that could provide additional prognostic information in Merkel cell carcinoma.

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas' score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Carbon ions therapy as single treatment in chordoma of the sacrum. Histologic and metabolic outcome studies.

OBJECTIVE: Even though carbon ions treatment (CIRT) of sacral chordoma (SC) substantially reduces tumor mass, tumor remnants are observed in most patients. Differentiating tumor remnants from necrosis is challenging, expensive in terms of imaging and time-consuming. So far, there has not been a systematic histological and metabolic analysis of post-CIRT lesions. We designed a prospective study aiming to histologically a metabolically differentiate between viable tumor and foci of necrosis and of fibrosclerosis after CIRT and correlate these findings to clinical outcome in patients with SC. PATIENTS AND METHODS: Between January 2013 and December 2016 18 patients, 12 males and 6 females, with histological confirmation of sacral chordoma, underwent CIRT. The total dose was 70.4 GyE, with a daily fraction of 4.4 GyE, for 4 weeks. MRI was performed every three months after treatment. FDG PET-CT scan and CT-guided needle biopsy were performed 6-12 months after CIRT. The incidence of complications (intraoperative and postoperative), local control (LC), overall survival (OS) and progression-free survival (PFS), changes in neurological status, clinical outcomes and toxicity were considered. RESULTS: All histological analysis but 2 reported signs of necrosis and of fibrosclerosis after CIRT. One of these 2 patients turned into a dedifferentiated chordoma. Radiological partial response (PR) was observed in 10 patients (56.3%) and stable disease (SD) in 5 patients (28.3). Two patients (11%) had a local relapse. The overall survival rate was 100% at 24 months. FDG PET CT after CIRT showed uptake decreasing compared with the baseline exam in all but one patient. CONCLUSIONS: The histological presence of necrosis and of fibrosclerosis after CIRT at the histological analysis supports the previous clinical evidence on the efficacy of CIRT. Volumetric stability of the residual mass should be considered as a success of treatment. In cases of a volumetric increase of the mass, a CT needle biopsy should always be performed. In our series, during the follow-up, the FDG-PET was able to promptly detect an increased uptake in the case which later was histologically defined as dedifferentiated chordoma.

A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.

The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG's consensus for the reporting of PitNETs and proposes a diagnostic algorithm.

Extra-axial chordoma: a clinicopathologic analysis of six cases.

Extra-axial chordoma is an exceedingly rare tumor, with only 28 cases reported in the literature to date. Axial and extra-axial chordoma exhibits complete morphologic and immunophenotypic (expression of brachyury) overlap. However, in consideration of the non-canonical presentation, extra-axial chordoma is under-recognized and often misdiagnosed, most often as extraskeletal myxoid chondrosarcoma or myoepithelioma. To increase our understanding of the clinicopathologic features of extra-axial chordoma, six cases have been retrieved from the files of the Istituto Ortopedico Rizzoli and of the General Hospital of Treviso. The clinicoradiologic, morphologic, and molecular features have been analyzed, and the follow-up was updated. Our series included four female and two male patients; their ages ranged from 20 to 67 years (mean 45.8 years). All patients presented with a single mass localized in four cases in the soft tissue (posterior arm, left leg, dorsal aspect of the foot, and popliteal fossa), and in two cases in the bone (radius and second metacarpal bone). Grossly, the neoplasm was lobulated, with a fleshy cut surface and a diameter ranging between 0.8 and 8 cm (mean 3.4 cm). Morphologically, all six cases showed an epithelioid cell proliferation organized in nests and cords demarcated by fibrous septa and set in an abundant extracellular myxoid matrix. Neoplastic cells featured hyperchromatic nuclei and abundant vacuolated cytoplasm. Immunohistochemically, all six cases were strongly positive for EMA, cytokeratin AE1/AE3, S100, and brachyury. INI1 nuclear expression was retained. Smooth muscle actin, calponin, p63, and GFAP were all negative. Fluorescent in situ hybridization (FISH) analysis did not reveal rearrangements involving NR4A3, FUS, and EWSR1 genes. At follow-up (mean 55 months), all patients were alive without disease after local surgical treatment. One patient underwent thigh amputation following multiple local recurrences and inguinal node metastases treated with marginal resection. In conclusion, primary extra-axial chordoma is an extremely rare neoplasm with distinct morphological and immunohistochemical features. Immunomorphology and molecular analysis allow distinction from both extraskeletal myxoid chondrosarcoma and myoepithelioma. Complete surgical resection appears to be curative.

Intralayer and interlayer electron-phonon interactions in twisted graphene heterostructures.

The understanding of interactions between electrons and phonons in atomically thin heterostructures is crucial for the engineering of novel two-dimensional devices. Electron-phonon (el-ph) interactions in layered materials can occur involving electrons in the same layer or in different layers. Here we report on the possibility of distinguishing intralayer and interlayer el-ph interactions in samples of twisted bilayer graphene and of probing the intralayer process in graphene/h-BN by using Raman spectroscopy. In the intralayer process, the el-ph scattering occurs in a single graphene layer and the other layer (graphene or h-BN) imposes a periodic potential that backscatters the excited electron, whereas for the interlayer process the el-ph scattering occurs between states in the Dirac cones of adjacent graphene layers. Our methodology of using Raman spectroscopy to probe different types of el-ph interactions can be extended to study any kind of graphene-based heterostructure.

Identification of lamivudine conformers by Raman scattering measurements and quantum chemical calculations.

Characterization of nucleoside and non-nucleoside human immunodeficiency virus (HIV) reverse transcriptase inhibitors conformers, NRTIs and NNRTIs, respectively, is fundamental for an improved treatment of infected individuals. Three conformers in lamivudine I powder are quickly identified in this work by assignment of some Raman peaks to their vibrational frequencies, as obtained by first principles quantum chemical calculations. The method is proposed as a practical procedure for non-destructive identification, analysis, and process monitoring of NRTIs and NNRTIs conformers.

Primary extraskeletal myxoid chondrosarcoma of bone: Report of three cases and review of the literature.

Extraskeletal myxoid chondrosarcoma is a rare neoplasm of soft tissue. The usual location is in deep parts of the proximal extremities and limb girdles in middle-aged adults. The bone location as primary location is extremely rare and few cases are reported. We present three cases arising in bone with molecular confirmation using both RT-PCR and FISH analysis. Patients include two men and one woman with an age of 62, 69 and 73 years old. The mean size of the lesion was 13cm (range 8-18cm). Tumors arose in the iliac bone in two cases and in the proximal humerus in the other case. At time of diagnosis the three cases show bone cortex and soft tissue involvement. On imaging, lesions have a lobular pattern, are purely lytic, but take up contrast medium after injection. Two patients are alive with disease (local recurrence and lung metastasis) after five years and five years and six months, respectively and one patient died of disease two years after the diagnosis. The primary extraskeletal myxoid chondrosarcoma of bone seems to have a more aggressive behavior than the soft tissue counterpart. The molecular confirmation of diagnosis using RT-PCR is necessary to do the differential diagnosis with other entities, in particular with myoepithelioma that shows similar morphological features and EWSR1 and FUS genes rearrangement.

Impact of residual disease after "unplanned excision" of primary localized adult soft tissue sarcoma of the extremities: evaluation of 452 cases at a single Institution.

BACKGROUND: Soft tissue sarcomas are often inappropriately excised; it is, however, still a matter of debate whether the presence of residual disease in the re-excision specimen can affect patients' prognosis. The aim of this study is to investigate the impact of re-excision after unplanned surgery of primary soft tissue sarcomas (STS) of the extremities. PATIENTS AND METHODS: We retrospectively evaluated 452 adults with grade 2-3, localized STS (349 primary and 103 unplanned excisions). RESULTS: In the re-excision group, a full 43% of the patients had residual tumor. The re-excision group achieved a significantly better outcome in terms of sarcoma-specific survival (SS) (p = 0.002), local recurrence (LR) (p = 0.004) and distant metastasis (DM) (p = 0.028). Residual tumor was associated with a higher risk of DM (p = 0.005). CONCLUSION: We confirm that unplanned surgery does not compromise patients' prognosis; scar re-excision guarantees at least the same SS, LR and DM rates compared to STS primarily treated in a referral center. Routine use of radiation therapy after re-excision could improve local control. Distant metastases seem to be negatively affected by the presence of residual tumor, and therefore, the use of CT in deep and large STS is suggested. The main goal is to avoid unplanned surgery by referring suspected lumps (especially deep, large, increasing in size) to a specialist center.

Dedifferentiated chondrosarcoma with "adamantinoma-like" features: A case report and review of literature.

Dedifferentiated chondrosarcoma is defined by the presence of a low grade malignant cartilaginous component juxtaposed to a high grade malignant non-cartilaginous sarcomatous components. Only 4 cases in which the high grade component showed epithelial differentiation have been reported in the literature; three featured a squamous and the one a glandular epithelial component. Here we describe a case of dedifferentiated chondrosarcoma exhibiting epithelial "adamantinoma-like" basaloid features. The patient underwent wide resection of the proximal tibia and post-operative chemotherapy and died 8 months after the diagnosis due to lung and bone metastases.

Histology and grading are important prognostic factors in synovial sarcoma.

INTRODUCTION: The diagnosis of synovial sarcoma (SS) is currently based on clinical, morphological, immunohistochemical and cytogenetic data. Some of these factors such as grade and histology, specific translocations (SS18-SSX1 vs. SS18-SSX2) and the reduced expression of INI1, were proposed as prognostic variables. The aim of this study was to verify whether histological (grading and histology) and molecular (type of SSX translocation and INI1 expression) characteristics of SS influence the prognosis of the disease. MATERIAL AND METHODS: We retrospectively evaluated 196 patients affected by SS of the extremities treated at our Institution (Istituto Ortopedico Rizzoli, Bologna, Italy). All cases were histologically revised and tumor grade was assessed according to the FNLCC system. Tissue specimens were retrospectively evaluated to check for SS18-SSX fusion type and INI1 expression. RESULTS: Most SS were monophasic, 28% were biphasic. Eighty tumors (41%) were grade 3. Sixty percent harbored SSX1 translocation, 40% SSX2; 51% maintained the expression of INI1. Sarcoma specific survival (OS) was 56.6% at 5 years and 46.9% at 10 years. Prognosis was worse in those patients monophasic SS (p = 0.011) as in those with a grade 3 tumors (p = 0.083). No correlation was found neither between SSX fusion type nor INI1 expression and survival. LR-free survival was 78.9% at 5 years and 75.9% at 10 years. A higher LR rate was observed in tumors with SSX2 translocation and (p = 0.049) in grade 3 SS (0 = 0.028). DISCUSSION: Our data confirm that not all cases of SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.

Surgical margins do not affect prognosis in high grade myxofibrosarcoma.

INTRODUCTION: Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas (STS) in elderly patients and it primarily affects the extremities. The aim of this retrospective analysis is to understand the natural history of MFS and whether adequate treatment influence prognosis. PATIENTS AND METHODS: We reviewed 129 adult patients with primary, localized, FNCLCC grade 3 MFS of the extremities operated at Istituto Ortopedico Rizzoli, Bologna. Sarcoma specific survival (SS), local recurrence (LR) and distant metastasis (DM) were analyzed. RESULTS: Among excised MFS (119), 106 (89.9%) had R0 margins, 13 (10.1%) R1 margins. No significant correlation between margins adequacy and tumor depth, location and size was found. Estimated SS was 73.2% at 5 years and 66.3% at 10 years, with a better SS in superficial MFS (p = 0.011). Local recurred MFS had a worse SS (p = 0.049). Local recurrence-free rate was 74.3% at 5 and 10 years. Even if not significant, a better outcome in term of LR was observed in superficial MFS and R0 margins. Distant metastasis-free survival was 75.6% at 5 years and 72.9% at 10 years, with a better outcome in superficial MFS (p = 0.012). DISCUSSION: Myxofibrosarcoma remain a debated entity with specific behavior features. Myxofibrosarcoma tends to local recur due to its infiltrative grow pattern making difficult to achieve "safe margins". To date, surgical margins as classified for other STS are not predictive of LR and patients' survival. Tumor grade and depth are still the most important prognostic factors.

Metastasizing tenosynovial giant cell tumour, diffuse type/pigmented villonodular synovitis.

Tenosynovial giant cell tumour, diffuse type, also known under a variety of other terms including diffuse pigmented villonodular synovitis, tends to be locally aggressive and not infrequently can show multiple recurrences. The differential diagnosis with the extremely rare and somewhat controversial malignant variant of tenosynovial giant cell tumour, diffuse type, is challenging due to overlapping radiologic features of these two entities. Malignant tenosynovial giant cell tumour is defined by the presence of overtly malignant sarcomatous areas. We describe a very unusual case of a 63-year-old man affected by tenosynovial giant cell tumour, diffuse type of the knee that, despite absence of morphologic evidence of sarcomatous transformation, developed inguinal lymph node metastases following multiple surgical procedures.

Sclerosing epithelioid fibrosarcoma of the thigh: report of two cases with synchronous bone metastases.

We report two cases of sclerosing epithelioid fibrosarcoma occurring in the deep soft tissue of the thigh, confirmed by molecular analysis and associated with bone metastases in the lumbar vertebrae and the iliac wing at the time of diagnosis. Synchronous bone metastases of sclerosing epithelioid fibrosarcoma are extremely difficult to diagnose because clinical and radiological features are not specific. In addition, the range of differential diagnoses is very wide, including metastatic carcinoma and osteosarcoma. At present, all but three published cases of sclerosing epithelioid fibrosarcoma with bone metastases showed bone metastases during follow-up. We confirm in our two cases that the distinct pattern of immunohistochemical staining for MUC4, associated with the absence of staining for both SATB2, a marker of osteoblastic differentiation, and pan-cytokeratin, allows differentiating between sclerosing epithelioid fibrosarcoma and metastatic carcinoma or osteosarcoma.

Are prions a relic of an early stage of peptide evolution?

The rather unique properties of prions and their presence in very different kinds of living species suggest that this type of molecule was created at a very early stage of evolution and may even represent a relic from a time where peptide evolution was ongoing and RNA/DNA did not yet exist. A comparison of the most frequently occurring amino acid sequences in known prions with the sequences preferentially formed in the salt-induced peptide formation reaction, the most simple mechanism enabling the formation of peptides under primitive earth conditions, shows a remarkable coincidence that strongly supports this hypothesis.