| Abstract | CILJ: Cilj istraživanja bio je učiniti citološko i morfometrijsko gradiranje citoloških uzoraka invazivnog karcinoma dojke i prosuditi mogućnost rutinske primjene citološkog gradiranja s ili bez morfometrijske analize, umjesto dosadašnje procjene gradusa tumora na histološkom materijalu; prosuditi reproducibilnost, konzistentnost i varijabilnost tehnike gradiranja među citolozima; te opisati biološku varijabilnost morfometrijskih parametara unutar i između gradusa, u svrhu optimalizacije i utvrđivanja minimalne, trenutno nedefinirane, veličine uzorka potrebite za morfometrijsku analizu. ISPITANICI I METODE: Istraživanjem je obuhvaćeno 45 ispitanica (15 po svakom gradusu) u kojih je dijagnoza karcinoma dojke postavljena na citološkim aspiratima dojke u OB „Dr. J. Benčević“ tijekom 2012. godine. Citološko gradiranje učinjeno je Robinsonovom metodom gradiranja, a određivanje histološkog gradusa korištenjem Elstonove modifikacije Bloom-Richardson-ove metode. Morfometrijska analiza provedena je programom SFORM. REZULTATI: Slaganje tri promatrača u određivanju citološkog gradusa i njegovoj komparaciji s histološkim gradusom procijenjeno je Kendall T-B testom. T vrijednosti iznosile su od 0,64 do 0,82. T vrijednosti između promatrača uzetog kao standard (promatrač s najvećim volumenom pregledanih uzoraka karcinoma dojke) i druga dva promatrača (interobserver varijabilnost) iznosile su od 0,45 do 0,85. Slaganje pojedinog promatrača pri ponovljenom citološkom gradiranju (intraobserver varijabilnost) iznosilo je od 0,57 do 0,79. Dijagnostička/prognostička vrijednost citološkog sustava gradiranja po Robinsonu i morfometrijska objektivizacija u određivanju gradusa invazivnog karcinoma dojke 81 SAŽETAK S porastom gradusa uočava se pad ekspresije progesteronskih receptora, značajan, stupnjeviti porast ekspresije proliferacijskog biljega Ki-67, viši pT stadij, te veći udio postmenopauzalnih ispitanica. Analizom razlika u distribuciji morfometrijskih parametara po gradusu izdvaja se značajan, stupnjevit porast mjerenih značajki s porastom gradusa. Gradus je odgovoran za prosječno tek 26, odnosno 35% varijance morfometrijskih obilježja stanice i jezgre. Glavninu varijance obilježja čine interindividualne razlike, odnosno heterogenosti među ispitanicima unutar gradusa, uz minimalne intraindividualne varijacije. Minimalnu, trenutno nedefiniranu, veličinu uzorka potrebitu za morfometrijsku analizu normirali smo na 100 stanica po uzorku, budući da ista jamči usku marginu greške. ZAKLJUČAK: Citološko gradiranje aspirata karcinoma dojke reproducibilno je i neovisno o iskustvu morfologa te dobro korelira s histološkim gradusom. Posljedično tome predstavlja koristan parametar u predviđanju histološkog gradusa, odnosno biološkog ponašanja tumora. Gradiranje morfometrijskom metodom statistički je značajno, ali zbog niskog udjela gradusa u varijanci morfometrijskih obilježja, odnosno širokog raspona preklapanja morfometrijskih parametara među gradusima, morfometrija kao metoda nema diskriminacijsku nego samo indikativnu sposobnost. |
| Abstract (english) | AIM: The aim of this study was to evaluate the cytological and morphometrical grading of breast cancer and to estimate the possibility of routine use of cytologic grading with or without morphometric analysis, instead of estimating the tumor grade only on histologic material; to estimate reproducibility, consistency and variability of grading techniques among cytologists and also to describe the biological variability of morphometric parameters within and between grades and to determine the minimum, currently undefined, of sample size required for morphometric analysis. MATERIAL AND METHODS: Forty five patients with histologically confirmed invasive breast carcinoma, treated in General Hospital Dr. J. Bencevic in 2012, were selected in the present study. Grading of breast carcinoma was done according to the Robinson’s method by three independent observers on two occasions. Histological grading was performed using Elston's modified Bloom Richardsons' scoring. Morphometric analysis was performed by means of the SFORM software. RESULTS: The agreement between observers in determining the cytological grade and it's comparison with histological grade was estimated with Kendall T-B test. T values ranged from 0.64 to 0.82. T values between standard observer (the one with highest volume of examined breast specimens) and the other two observers (interobserver varability) ranged from 0.45 to 0.85 for cytological grading. Agreement between the individual observer at the repeated cytological grading (intraobserver variability) ranged from 0.57 to 0.79. Dijagnostička/prognostička vrijednost citološkog sustava gradiranja po Robinsonu i morfometrijska objektivizacija u određivanju gradusa invazivnog karcinoma dojke 83 SUMMARY With increasing tumor grade we observed the decrease of progesterone receptors expression , significant increase in the expression of the proliferation marker Ki-67, higher pT stage, and large proportion of postmenopausal women. By analyzing differences in the distribution of morphometric parameters by grade we observed a significant, gradual increase in the measured characteristics with increasing grade. Gradus is responsible for an average of 26 or 35% of the variance of morphometric characteristics of cells and nuclei. The majority of the variance features make interindividual differences or heterogeneity among respondents within the grade. Minimal sample size which is currently undefined and not standardized and was needed for morphometric analysis, was normalized to 100 cells per sample, since the same guarantees a narrow margin of error. CONCLUSION: Cytological grading of aspirates of breast cancer is reproducible and independent of experience of morphologist and correlates well with established histological grade and as such can be predictor of histologic grade and provide relevant information about the biological behavior of invasive breast cancer. Morphometric grading method is statistically significant but due to low proportion of grade in variance of morphometric features and a wide range of overlapping morphometric parameters among grades differences, morphometry as a method does not have discriminatory but just indicative capacity. |
