Aims. The aim of the study was to determine cellular ploidy of invasive ductal breast carcinoma with neuroendocrine (NE) differentiation and its share in certain phases of the cell cycle. It was also aimed at assessing the relationship of the cell cycle profile with other clinical and histopathological features.
Methods. The study was carried out in 80 patients with invasive ductal breast cancer, and classified as breast carcinoma with NE differentiation according to their histopathological parameters. The patients underwent treatment at the University Hospital for Tumors, Zagreb, Croatia during the period January 1 to December 31, 1992. Data about patients’ age, estrogen and progesterone receptor concentration, cancer size, and treatment modality were retrospectively collected from their case histories. Paraffin blocks were used for immunohistochemical and histochemical analysis and flow cytometric analysis of the tumor cell cycle. Neuroendocrine tumor diagnosis was made using Grimelius and immunohistochemical staining including neuron-specific enolase (NSE), chromogranin A and synaptophysin.
Results. Analysis by flow cytometry detected 27 tumors (33.8%) with DNA diploidy showing proliferative activity lower than 20%, and 53 tumors (66.2%) with DNA aneuploidy, tetraploidy and/or DNA diploidy with proliferative activity over 20%. Progesterone receptor concentration in DNA-diploid tumors was significantly higher that in DNA-aneuploid, tetraploid tumors and tumors with proliferative activity of ≥20% (p<0.001). Concentration of estrogen receptors, age, histological grade, tumor size, Grimelius staining and immnohistochemical markers did not significantly differ between the groups.
Conclusion. Data collected in our study show a higher mean concentration of progesterone receptors in the group of diploid tumors and tumors with low proliferative activity. In consideration with the above criterium, other pathological and clinical parameters did not show any significant difference relative to both tumor ploidy and its proliferative activity. For final conclusion on the clinical significance of neuroendocrine differentiation in breast cancer further studies that would include monitoring of the course and outcome of the disease are required.Ciljevi. Cilj našeg istraživanja bio je odrediti ploidnost stanica kod invazivnih duktalnih karcinoma dojke s neuroendokrinom (NE) diferencijacijom i njihov udio u pojedinim fazama staničnog ciklusa. Također se htjelo utvrditi povezanost profila staničnog ciklusa s drugim kliničkim i patohistološkim značajkama.
Metode. Istraživanje je provedeno na 80 bolesnica s duktalnim invazivnim karcinomom dojke koji su prema patohistološkim parametrima svrstani u karcinome dojke s NE diferencijacijom. Bolesnice su liječene u razdoblju od 01.01. do 31.12.1992. godine na Klinici za tumore u Zagrebu. Podaci o dobi bolesnica, koncentraciji estrogenskih i progesteronskih receptora, veličini karcinoma, te načinu liječenja dobiveni su retrospektivno iz povijesti bolesti. Parafinski blokovi upotrijebljeni su za imunohistokemijsku i histokemijsku analizu te analizu staničnog ciklusa tumorskih stanica protočnom citometrijom. Dijagnoze neuroendokrinih tumora postavljene su na temelju bojenja po Grimeliusu te imunohistokemijskih bojenja uključujući neuron-specifičnu enolazu (NSE), kromogranin A i sinaptofizin.
Rezultati. Protočnom citometrijom kod 27 tumora (33.8%) nađena je DNA diploidija i visina proliferativne aktivnosti manja od 20%, dok su DNA aneuploidija, tetraploidija i/ili DNA diploidija s proliferativnom aktivnošću većom od 20% nađene kod 53 tumora (66.2%). Koncentracija progesteronskih receptora u DNA-diploidnim tumorima bila je značajno viša nego kod DNA-aneuploidnih, tetraploidnih i tumora s proliferativnom aktivnošću ≥20% tumora (p<0.001). Koncentracija estrogenskih receptora, dob, histološki stupanj, veličina tumora, bojanje po Grimeliusu te imunohistokemijski markeri nisu se značajno razlikovali u ove dvije skupine.
Zaključak. Podaci iz našeg istraživanja upućuju na veću prosječnu koncentraciju progesteronskih receptora u skupini diploidnih tumora i tumora s niskom proliferativnom aktivnošću. Prema navedenom kriteriju drugi patološki i klinički parametri nisu pokazali značajnu razliku u odnosu na ploidnost i proliferativnu aktivnost. Za donošenje konačnog zaključka o kliničkoj važnosti neuroendokrine diferencijacije kod karcinoma dojke potrebno je provesti istraživanja koja bi uključila praćenje tijeka i ishoda bolesti
