Napovedni pomen semikvantitativnega in kvantitativnega določanja proliferacijske aktivnosti pri raku dojke

Đokić, Snežana (avtor), Jeruc, Jera (mentor)

Proliferacijska aktivnost (PA) je pomemben prognostični in prediktivni dejavnik pri karcinomu dojke. Klub temu, da je Ki-67 priznan označevalec PA v histoloških rezinah, je njegova uporaba v klinični praksi še vedno vprašljiva zaradi nestandardiziranih metod ocenjevanja in neenotne mejne vrednosti, ki bolnice razdeli v prognostične skupine. V nalogi smo validirali tri metode ocenjevanja PA na histoloških vzorcih raka dojke ter preverili njihovo klinično uporabnost. Pri 411 bolnicah s primarnim zgodnjim rakom dojke smo trije patologi, dva usmerjena in eden z malo izkušnjami, na tkivnih rezinah ocenili delež Ki67-pozitivnih jeder tumorskih celic s tremi različnimi metodami in rezultat primerjali z objektivno metodo, deležem tumorskih celic v fazi S celičnega cikla (SPF) v vzorcih istih bolnic, dobljenih z aspiracijsko biopsijo s tanko iglo. Pokazali smo dobro ujemanje ter zmerno korelacijo med kvantitativno metodo SPF in vsako od treh metod določanja PA z Ki-67, pri čemer so bile vrednosti PA ocenjene s Ki-67 višje od PA izmerjene s SPF. Korelacija med posameznimi metodami ocenjevanja Ki-67 je bila zelo dobra. Rezultati so pokazali odlično ujemanje med tremi patologi za vse tri metode ocenjevanja PA iz tkivnih rezin z vrednostjo intraklasnega koeficienta korelacije nad 0,90, kar kaže na zelo visoko ponovljivost znotraj laboratorija. Ujemanje je bilo najboljše pri uporabi semikvantitativne vizualne metode, ki je tudi najbolj enostavna za uporabo v klinični praksi. Analiza klinično-patoloških parametrov je pokazala, da so imele bolnice z visokim Ki-67 (?30%) bistveno večji delež karcinomov, ki so bili gradusa 3, ER-negativni in višjega stadija bolezni, kar se je odražalo tudi v krajšem času do ponovitve bolezni v prvih letih spremljanja. Večina bolnic z visoko PA je imela recidive v prvih petih letih, bolnice z nizko PA pa praviloma po petih letih. Bolnice s hormonsko odvisnimi karcinomi v zgodnjem stadiju z nizko PA (?10%) in tudi tiste s srednje visoko PA (?20%) , zdravljene le z hormonsko terapijo, so imele podobno preživetje kot bolnice, zdravljene s kemoterapijo. Iz prve slovenska študije, ki je validirala metode vrednotenja PA s Ki-67 lahko zaključimo, da je vizualna ocena Ki-67 zanesljiva in enostavna metoda, ki dobro korelira s kvantitativnimi metodami in kaže največjo ponovljivost med raziskovalci. Semikvantitativno določena PA je pomemben dejavnik pri oceni prognoze in tudi pri odločitvah o zdravljenju, predvsem v skupini bolnic s hormonsko odvisnimi tumorji.

• Jezik: Slovenski jezik
• Ključne besede: karcinom dojke, proliferacijska aktivnost, Ki-67, MIB-1, frakcija S-faze, proliferacija, napovedni dejavnik.
• Vrsta gradiva: Doktorsko delo/naloga
• Organizacija: MF - Medicinska fakulteta
• Leto izida: 2025
• PID: 20.500.12556/RUL-168586
• Datum objave v RUL: 18.04.2025

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: The prognostic significance of semiquantitative and quantitative assessment of proliferative activity in breast cancer

Izvleček

Proliferative activity (PA) is an important prognostic and predictive factor in breast cancer. Although Ki-67 is a recognised marker of PA in histological sections, its use in clinical practice is still questionable due to non-standardised assessment methods and an inconsistent cut-off value that divides patients into prognostic groups. In this study, we validated three PA assessment methods on of breast cancer histological samples and evaluated their clinical applicability. In 411 patients with early-stage primary breast cancer, three pathologists, two experienced and one less experienced, assessed the proportion of Ki67-positive tumor cell nuclei on tissue sections using three different methods. The results were compared to an quantitative method – the proportion of tumor cells in the S phase of the cell cycle (SPF) in fine-needle aspiration biopsy samples from the same patients. We demostrated good agreement and moderate correlation between the quantitative SPF method and each of the three methods for determining PA by Ki-67, with PA values estimated by Ki-67 being higher than PA measured by SPF. The correlation between the individual methods of estimating Ki-67 was very good. The results showed excellent agreement between the three pathologists for all three methods of PA estimation with Ki-67 with an intraclass correlation coefficient of over 0.90, indicating very high intra-laboratory reproducibility. The best agreement was obtained with the semi-quantitative visual method, which is also the most practical for use in clinical practice. Analysis of clinicopathological parameters showed that patients with high Ki-67 (≥30%) had a significantly higher proportion of grade 3, estrogen receptor-negative and high stage tumors, which was also reflected in a shorter time to recurrence during the first years of follow-up. In most patients with high PA, recurrences occurred within the first five years, whereas in patients with low PA, recurrences usually occurred after five years. In patients with hormone-dependent early-stage cancer with low PA (up to 10%) as well as those with intermediate PA (up to 20%) treated with hormone therapy alone, the time to recurrence was similar to that of patients treated with chemotherapy. From the first Slovenian study in which Ki-67 PA assessment methods were validated, we can conclude that visual assessment of Ki-67 is a reliable and simple method that correlates well with quantitative methods and has the highest reproducibility among pathologists. PA determined by visual assessment is an important prognostic factor of breast cancer, which also influences treatment decisions, especially in the group of patients with hormone-dependent tumors.

• Ključne besede: breast carcinoma, proliferative activity, Ki-67, MIB-1, S-phase fraction, proliferation, a prognostic factor