HER2

Durante la biopsia viene prelevato un campione di cellule o di tessuto che sarà successivamente esaminato al microscopio.

Solitamente, viene somministrato al paziente un anestetico locale o generale. Nel caso dell'anestesia generale viene indotto nel paziente uno stato di incoscienza, inibendo la sensibilità al dolore.

La preparazione al test dipende dal tipo di biopsia che viene eseguita, stabilito in base all'area in cui viene prelevato il campione di tessuto.

Nel caso in cui l'esecuzione della biopsia richieda soltanto la somministrazione di un anestetico locale, non sono generalmente previste particolari preparazioni prima di sottoporsi al prelievo.

Nel caso in cui il paziente necessiti di una biopsia chirurgica, che prevede l'esecuzione in anestesia generale o in sedazione, può essere richiesto il digiuno (è permesso solo bere acqua) prima di sottoporsi alla procedura. 

Indipendentemente dalla tipologia di procedura utilizzata, è necessario attenersi a tutte le istruzioni fornite.

Tumore della mammella

Il test HER2 viene eseguito in persone alle quali vengano diagnosticati tumori della mammella invasivi o ricorrenti. Infatti, i pazienti affetti da tumori HER2-positivi possono trarre beneficio dall'utilizzo della terapia mirata (targeted therapy) contro HER2.

Il test può avere anche una valenza prognostica, fornendo informazioni circa l'aggressività del tumore. Non si tratta di un test diagnostico, ma fornisce comunque al clinico molte informazioni utili riguardo le caratteristiche del tumore e la valutazione delle strategie terapeutiche più appropriate. I tumori HER2-positivi tendono a crescere in maniera più aggressiva e, nel caso dei tumori alla mammella, sono resistenti alle terapie endocrine (anti-ormonali) e ad alcuni tipi di chemioterapia standard. Le persone affette da tumori HER2-positivi tendono ad avere una prognosi peggiore, anche se questa caratteristica consente l'utilizzo di una terapia mirata (targeted therapy) specifica per questo tipo di tumori.

Il test HER2 viene di solito richiesto insieme al test per il recettore degli estrogeni e progesterone. Insieme, i risultati di questi test forniscono indicazioni prognostiche importanti per la scelta degli approcci terapeutici più appropriati.

Tumore all'esofago e allo stomaco (gastroesofageo)

Per i pazienti affetti da tumori gastroesofagei inoperabili, in stadio avanzato, ricorrenti o metastatici candidati per l'utilizzo della terapia mirata contro HER2, viene raccomandata l'esecuzione del test per stabilire l'eventuale overespressione di HER2 e quindi stabilire se farmaci come il trastuzumab potrebbero essere efficaci.

Questo test viene raccomandato, insieme ad altri test come quello per il recettore degli estrogeni e progesterone, come parte della valutazione del tumore invasivo della mammella.

Inoltre, il test viene raccomandato nei seguenti casi:

• Pazienti affetti da tumori metastatici, ossia diffusi in altre aree dell'organismo
• Pazienti affetti da tumori ricorrenti, ovvero che si ripresentano in seguito al trattamento efficace del tumore
• Pazienti affetti da adenocarcinomi dello stomaco o dell'esofago inoperabili, ricorrenti o metastatici, candidati per la terapia mirata contro HER2.

Tumore della mammella

L'immunoistochimica (IHC) viene spesso utilizzata per determinare lo stato di HER2 in pazienti affetti da tumori alla mammella invasivi, metastatici e ricorrenti. Al test viene assegnato un punteggio che varia da 0 a 3, in base al quale si definisce lo stato di HER2 come segue:

• IHC 3+: HER2-positivo
• IHC 2+: dubbio
• IHC 1+: HER2-negativo
• IHC 0: HER2-negativo

Un tumore alla mammella HER2-positivo è con buona probabilità un tumore aggressivo, non rispondente alla terapia ormonale e resistente alla chemioterapia standard. Tuttavia, le persone affette da questo tipo di tumore possono beneficiare della terapia mirata con farmaci come trastuzumab, lapatinib o pertuzumab.

Se il test risulta negativo o dubbio con un metodo (immunoistochimica o FISH), allora deve essere eseguito anche l'altro metodo. Nel caso in cui il secondo metodo fornisca un risultato positivo, allora la persona è candidata per la terapia mirata.

Nel caso in cui venga invece confermato un risultato negativo con entrambi i metodi, allora il paziente non deve essere trattato con i farmaci sopramenzionati, che risulterebbero inefficaci e comporterebbero solo la comparsa degli effetti avversi correlati alla tossicità del trattamento.

Tumore allo stomaco e all'esofago

L'utilizzo della terapia mirata contro HER2 nelle persone affette da tumori allo stomaco e/o all'esofago in stadio avanzato e HER2-positivi può aumentarne la sopravvivenza e migliorare la qualità della vita.

Nel caso in cui il risultato sia negativo o dubbio all'immunoistochimica, allora deve essere eseguita anche la FISH. Nel caso in cui la FISH sia positiva, il tumore viene classificato come HER2-positivo.

Nel caso in cui invece il risultato sia negativo con entrambi i metodi, il tumore viene classificato come HER2-negativo.

Talvolta, i risultati del test possono essere dubbi per l'inadeguatezza del campione. In questo caso è necessario ripetere il test su un altro campione di tessuto tumorale.

Il test HER2 potrebbe non essere disponibile ovunque. Sia l'immunoistochimica che la FISH sono metodiche per le quali viene richiesto personale esperto per l'esecuzione ed interpretazione dei risultati. Il campione tumorale, quindi, potrebbe essere spedito presso un laboratorio lontano dalla sede nella quale viene eseguita la biopsia ed il risultato del test potrebbe essere ricevuto dopo alcune settimane.

Non tutti i tumori HER2-positivi sono sensibili alla terapia mirata con tutti i farmaci anti-HER2. Questi possono essere utilizzati da soli o in associazione con chemioterapici. Nel caso in cui un farmaco non risulti efficace, può essere tentato l'utilizzo di un altro farmaco per la terapia mirata.

Esiste anche un test per la misura di HER2 nel sangue, ma al momento non esiste consenso nella comunità scientifica circa il suo utilizzo e pertanto non viene raccomandato.

Nelle fasi iniziali degli approfondimenti diagnostici riguardanti il tumore alla mammella può essere richiesto anche il test per il recettore degli estrogeni e progesterone. I tumori positivi a questo test potrebbero rispondere peggio alla terapia ormonale nel caso in cui risultassero anche HER2-positivi. Inoltre, il clinico può richiedere l'esecuzione del profilo di espressione genica per il carcinoma della mammella per ottenere maggiori informazioni riguardo le caratteristiche del tumore.

Sfortunatamente no. Tuttavia, la terapia mirata contro HER2 può essere combinata con agenti chemioterapici con lo scopo di migliorarne l'efficacia.

Sì, gli uomini hanno un’incidenza di carcinoma mammario minore rispetto alle donne, ma tra i pochi pazienti affetti possono esservi casi HER2-positivi. Le linee guida raccomandano l'esecuzione del test in tutti i pazienti, indipendentemente dal genere, candidati per la terapia mirata contro HER2.

Il test HER2 viene considerato un test affidabile per la valutazione dei pazienti con tumore alla mammella, allo stomaco e all'esofago. Tuttavia, diversi fattori possono influenzare l’accuratezza del test:

• Metodi di laboratorio: poiché esistono varie metodologie per valutare lo stato di HER2, possono essere rilevate variazioni nei risultati in relazione alle tecniche di laboratorio utilizzate e alla processazione del campione tumorale
• Numero di campioni tumorali analizzati: nel caso di pazienti affetti da tumore allo stomaco e da alcuni tipi di tumore all'esofago, è consigliabile il prelievo di più campioni durante la biopsia. Infatti, l'analisi di un singolo campione potrebbe non rilevare la presenza di cellule tumorali HER2-positive.

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Gregory J. Tsongalis, PhD, HCLD, CC, Professor of Pathology, Director, Molecular Pathology, Dartmouth Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH.