Cytokeratin expression in breast cancer: Phenotypic changes associated with disease progression

Abstract

Transition from a normal to a cancerous state is marked by alterations in the cytoskeletal structure of those cells involved. We have examined such changes to determine if these transitions are markers of disease progression. Cytokeratin (CK) protein and messenger RNA (mRNA) expression were examined in malignant and benign breast tissues. Flow cytometric results demonstrated a significant correlation between cytokeratin protein expression detected by 5D3 antibody, specific for cytokeratins 8, 18, and 19 and axillary node metastasis (P = 0.01). A threshold of positivity of 338,000 molecules/cell was determined and reflected the wide range in cytokeratin levels expressed by normal or benign tissues. Examination of cytokeratins 8, 18, and 19 revealed a consistent pattern of expression with respect to tumor grade. Only cytokeratin 19 showed significant correlation with increasing tumor size (P = 0.006). mRNA expression for cytokeratin 8 was significantly higher in node-positive compared with node-negative disease (P = 0.02). Cytokeratin 18 mRNA levels were significantly lower in both node-negative (P = 0.03) and node-positive (P = 0.02) patients when compared with benign samples. Increased levels of cytokeratin 18 mRNA showed an inverse relationship with protein expression (P = 0.05). The results indicate that cytokeratin expression in breast cancer may be associated with tumor progression. Furthermore, the alteration in the expression of individual cytokeratins deserves further investigation to determine the consequences of these changes with respect to cellular function.

Cytoskeletal and extracellular matrix proteins as markers for metastatic triple negative breast cancer

“…However, some previous studies have stated that CK-18 was upregulated in breast cancer tissues, while other studies mentioned that CK-18 was downregulated in breast cancer tissues compared with normal tissues. [26][27][28][29] In this study, all tissues diagnosed as stages 2B, 3A, and 3B were positive for CK-18, while in stage 3C, some tissues were negative and some were positive with insignificant variation. However, different studies have concluded that aggressive or advanced-stage cancers are associated with loss of cytokeratin.…”

Cuantificación de ADN y CK18 por citometría de flujo multiparamétrica en el cáncer de mama inicial en el tumor primario y ganglios centinelas. Valor pronóstico a largo plazo

“…No tenemos una explicación para el único caso en el que la expresión de CK18 en el GC fue inferior, aparte de que podría haber sido uno de los clones metastásicos el que infiltrara el GC. De hecho, se ha descrito la pérdida de expresión de CK18 (o el descenso de la misma) como reflejo de la transformación neoplásica celular (282). En cuanto a los casos en los que la expresión de CK18 se incrementó no podemos descartar que se trate de una cuestión relacionada con que, al ser menor la cantidad de células tumorales, la competición por las moléculas del anticuerpo descienda, con el correspondiente incremento de la señal de fluorescencia.…”

Ανάπτυξη Και Κλινικές Εφαρμογές Μεθόδων Μοριακής Διαγνωστικής Για Την Ανίχνευση Κυκλοφορούντων Καρκινικών Κυττάρων Στον Καρκίνο Του Μαστού Μέσω Της Έκφρασης Της Μαστοσφαιρίνης Α

“…[190]. Τροποποίηση της έκφρασης των κυτταροκερατινών κατά τη διάρκεια της καρκινικής εξέλιξης έχει επίσης περιγραφεί [191,192]. H φαινοτυπική ετερογένεια των [196].…”