Molecular Phenotypes of Unifocal, Multifocal, and Diffuse Invasive Breast Carcinomas

We analyzed the subgross distribution of the invasive component in 875 consecutive cases of breast carcinomas using large-format histology sections and compared the immunophenotype (estrogen and progesterone receptor expression, HER2 overexpression and expression of basal-like markers, CK5/6, CK14, and epidermal growth factor receptor) in unifocal, multifocal, and diffuse tumors. Histology grade and lymph node status were also analyzed. Unifocal invasive carcinomas comprised 58.6% (513/875), multifocal invasive carcinomas 36.5% (319/875), and diffuse invasive carcinomas 4.9% (43/875) of the cases. The proportion of lymph node-positive cases was significantly higher in multifocal and diffuse carcinomas compared to unifocal cancers, but no other statistically significant differences could be verified between these tumor categories. Histological multifocality and diffuse distribution of the invasive tumor component seem to be negative morphologic prognostic parameters in breast carcinomas, independent of the molecular phenotype

LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-Type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.Fil: Lindquist, David. Universidad de Umea; SueciaFil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Herdenberg, Carl. Universidad de Umea; SueciaFil: Larsson, Catharina. Karolinska University Hospital;Fil: Höppener, Jo. University Medical Center Utrecht;Fil: Wang, Na. Karolinska University Hospital;Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tarján, Miklós. Falu Lasarett; SueciaFil: Tot, Tibor. Falu Lasarett; SueciaFil: Henriksson, Roger. Universidad de Umea; SueciaFil: Hedman, Håkan. Universidad de Umea; Sueci

Glukokortikoid receptor gén polimorfizmusok és a primer és szekunder osteoporosis összefüggéseinek vizsgálata = Association between glucocorticoid receptor gene polymorphisms and primary and secondary osteoporosis

A glükokortikoid receptor gén három polimorfizmusának összefüggését vizsgáltuk az osteoporosisos hajlammal normál populációban valamint szteroid-indukált osteoporosisos betegekben. Kidolgoztunk két új allélspecifikus PCR módszert (J Steroid Biochem Mol Biol., 92:465-8 és J Steroid Biochem Mol Biol., 100:161-6). Eredményül azt találtuk, hogy a normál populációt reprezentáló 241 személyben, akiknek anamnézisében a csontot befolyásoló betegség vagy kezelés nem szerepelt, az N363S variáns hordozása a csont metabolizmus lebontás irányba való eltolódásával járt (p=0,042; r=0,73). A csont denzitásra az N363S polimorfizmus nem volt szignifikáns hatással, feltehetően a vizsgált betegcsoport széles korösszetétele miatt. A BclI és ER22/23EK polimorfizmusok nem befolyásolták sem a csontanyagcserét, sem a csont ásványi anyag tartalmát (ezen eredményeinket közlő kézirat jelenleg elkészítés alatt van). A 36 szteroid-indukált osteoporosisos betegben a polimorfizmusok előfordulása nem tért el szignifikánsan az egészségesektől, azonban megjegyzendő, hogy az N363S variáns allélfrekvenciája háromszor magasabb volt a normál populációban mértnél (0,09 vs. 0,03, p=0,097), így tervezzük ennek a tendenciának további vizsgálatát. Eredményeink azt mutatják, hogy a glükokortikoid receptor érzékenységét növelő N363S polimorfizmus a normál populációban intenzívebb csont lebontásra hajlamosít. Ez hosszú távon a csont minőségének romlásához és osteoporosis kialakulásához vezethet. | We investigated the role of three polymorphisms of the glucocorticoid receptor gene in osteoporotic tendency of normal subjects and patients with steroid-induced osteoporosis. We elaborated two new methods based on allele-specific PCR (J Steroid Biochem Mol Biol., 92:465-8 and 100:161-6). We found that among the 241 patients who have never had any disease or medication influencing bone health, the N363S variant was associated with an increased rate of bone resorption (p=0,042; r=0,73). The N363S polymorphism did not influence bone mineral density in these subjects, possibly due to the wide age range of the studied population. The BclI and ER22/23EK polymorphisms did not influence neither bone metabolism, nor bone mineral density (our manuscript publishing these results is in preparation). In the 34 patients with steroid-induced osteoporosis, the frequency of the three polymorphisms did not differ significantly from the normal population. Nevertheless, allele frequency of the N363S variant was three times higher in steroid-induced osteoporotic patients than in healthy subjects (0,09 vs. 0,03, p=0,097), and we plan further studies to investigate this tendency. In conclusion, our results suggest that the N363S polymorphism of the glucocorticoid receptor gene is associated with an increased rate of bone resorption in the normal population. This increased bone resorption could lead on the long-term to the impairment of bone quality and a tendency to osteoporosis

Hörselskydd i livemusikbranschen, ett krav eller ett hjälpmedel? : En kvantitativ studie om dämpningskvalitet hos hörselskydden från Bellman & Symfon.

I den här uppsatsen undersöker jag dämpningskvaliteten hos Bellman & Symfon hörselskydd, mer specifikt Bellman ER 9- och ER 15-modellen. Frågor som uppsatsen besvarar är hur dämpningskurvan ser ut, vad skillnaden är mot företagets mätningar och varför det inte finns några mätningar över 8000 Hz. Som metod valdes experiment för att ge svar på forskningsfrågorna. För noggrannare mätningar skapades ett öra. Under mätningarna användes både enskilda sinustoner och brus. Resultatet visar att båda hörselskydden har en ganska lika frekvenskurva. Frekvenserna mellan 750 Hz och 3000 Hz sticker ut där dämpningen är mindre än vid resterande frekvenser. Både ER 9 och ER15 har en liknande frekvenskurva, där bas och diskant har en kraftigare dämpning än Bellman & Symfons mätningar och mellanregistret är mindre dämpat. Resultatet visar också att frekvenserna över 8000 Hz är instabila och utsläckningar förekommer

A klinikai diagnózis és a kórbonctani lelet összehasonlításának módszerei és buktatói = Discrepancies between clinical and pathological diagnoses, methods and pitfalls

A szerzők követték a klinikai és kórbonctani diagnózisok összehasonlításának menetét. Saját anyaguk és irodalmi adatok alapján vizsgálták a halál alapjául szolgáló betegség megállapítását, valamint az összehasonlításukat zavaró, megnehezítő tényezőket és ezek kiküszöbölésének lehetőségeit. Javasolják, hogy a klinikai és kórbonctani diagnózisok összehasonlítására olyan módszert válasszanak, melyek az eltérések természetét és azok okainak elemzését is lehetővé teszik. Az összevetés csakis egységes elvek alapján feldolgozott, ellenőrzött anyag esetében reális, az eredményeket körültekintően kell interpretálni. | The authors followed the procedure of comparison of clinical and pathological diagnoses. Based on their own data and those from the literature, they examined the diagnostic difficulties of the underlying cause of death, the disturbing factors in the comparison of clinical and pathological diagnoses, and the possibility of resolving them. They suggest to choose a method of comparison which can offer the possibility of analyzing both the nature and causes of discrepancies. This comparison can be realistic only if these issues are studied with the same and uniform method, and the results must be interpreted cautiously

Comparison of the Subgross Distribution of the Lesions in Invasive Ductal and Lobular Carcinomas of the Breast: A Large-Format Histology Study

To compare the lesion distribution and the extent of the disease in ductal and lobular carcinomas of the breast, we studied 586 ductal and 133 lobular consecutive cancers. All cases were documented on large-format histology slides. The invasive component of ductal carcinomas was unifocal in 63.3% (371/586), multifocal in 35.5% (208/586), and diffuse in 1.2% (7/586) of the cases. The corresponding figures in the lobular group were 27.8% (37/133), 45.9% (61/586), and 26.3% (35/133), respectively. When the distribution of the in situ and invasive component in the same tumors was combined to give an aggregate pattern, the ductal carcinomas were unifocal in 41.6% (244/586), multifocal in 31.6% (185/586), and diffuse in 26.8% (157/586) of the cases. The corresponding figures in the lobular category were 15.0% (20/133), 54.2% (72/133), and 30.8% (41/133), respectively. Ductal cancers were extensive in 45.7% (268/586), lobular in 65.4% (87/133) of the cases. All these differences were statistically highly significant (). While the histological tumor type itself (ductal versus lobular) did not influence the lymph node status, multifocal and diffuse distribution of the lesions were associated with significantly increased risk of lymph node metastases in both ductal and lobular cancers

Skull base chordoma mimicking a preauricular neoplasm in a child: Clinicopathological features and biological behaviour

Introduction: The extreme rarity of chordomas in childhood, the slow growing nature of these tumours and the diverse symptoms may cause many diagnostic problems. Patient: A 9-year-old girl presented with an unusual manifestation of a skull base chordoma. The clinical and pathological features were analysed. Result: In the present case, the initial symptoms of the skull base tumour were completely misleading. The otodynia, the masticatory difficulties and the mass in the preauricular region were not characteristic of skull base chordomas. The female sex, the young age, the large tumour size and the atypical histological pattern of the tumour all indicated a very poor prognosis. Conclusion: The rarity of this tumour in childhood and the atypical lateral and intracranial spread resulted in a serious delay of the diagnosis and in a fatal outcome

A Proposal to Unify the Classification of Breast and Prostate Cancers Based on the Anatomic Site of Cancer Origin and on Long-term Patient Outcome

The similarity between the structure and function of the breast and prostate has been known for a long time, but there are serious discrepancies in the terminology describing breast and prostate cancers. The use of the large, thick-section (3D) histology technique for both organs exposes the irrationality of the breast cancer terminology. Pathologists with expertise in diagnosing prostate cancer take the anatomic site of cancer origin into account when using the terms AAP (acinar adenocarcinoma of the prostate) and DAP (ductal adenocarcinoma of the prostate) to distinguish between the prostate cancers originating primarily from the fluid-producing acinar portion of the organ (AAP) and the tumors originating either purely from the larger ducts (DAP) or from both the acini and the main ducts combined (DAP and AAP). Long-term patient outcome is closely correlated with the terminology, because patients with DAP have a significantly poorer prognosis than patients with AAP. The current breast cancer terminology could be improved by modeling it after the method of classifying prostate cancer to reflect the anatomic site of breast cancer origin and the patient outcome. The long-term survival curves of our consecutive breast cancer cases collected since 1977 clearly show that the non-palpable, screen-detected breast cancers originating from the milk-producing acini have excellent prognosis, irrespective of their histologic malignancy grade or biomarkers. Correspondingly, the breast cancer subtypes of truly ductal origin have a significantly poorer outcome, despite recent improvements in diagnosis and therapy. The mammographic appearance of breast cancers reflects the underlying tissue structure. Addition of these “mammographic tumor features” to the currently used histologic phenotypes makes it possible to distinguish the breast cancer cases of ductal origin with a poor outcome, termed DAB (ductal adenocarcinoma of the breast), from the more easily managed breast cancers of acinar origin, termed AAB (acinar adenocarcinoma of the breast), which have a significantly better outcome. This simple and easily communicable terminology could lead to better communication between the diagnostic and therapeutic team members and result in more rational treatment planning for the benefit of their patients