ACC is well-known for its indolent growth but common recurrence and late distant metastasis. Although the 5-year survival rate is high, 10-year and 15-year survival markedly decreased. Hence, it is classified as “high risk” by the World Health Organization . The classic treatment is complete resection followed by postsurgical radiotherapy. In our study, 3 of 80 patients gave up surgery on initial diagnosis and underwent radiotherapy alone. The tumor developed gradually. The other 77 cases underwent surgery and postsurgical radiotherapy but no chemotherapy. The 5-year and 10-year survival was 66.41% and 10.16%, respectively, results which vary greatly from some reported literature.
In 2005, the World Health Organization reported an extremely low survival rate of ACC. Five-year and 10-year survival rates of ACC in the salivary gland were 35% and 10%, respectively. Ten-year survival in the sinonasal subsite was 7%. The 10-year survival was similar to that in our data, but the 5-year survival was much lower. It was speculated that the cited data came from earlier literature (1974, 1978, 1990), when both the treatment and patient health care were different from today, which eventually caused difference in 5-year survival [1, 3, 4]. However, ACC is characterized by endless growth and late distant metastasis. It is radiosensitive but cannot be cured by radiation alone. When surgery is unavailable due to recurrence or metastasis, the outcome is poor. This is why the 10-year survival rate was similarly low.
However, Ellington CL et al. has reported an extremely high survival of ACC in 2012, with the 5-year, 10-year and 15-year survival being 90%, 80% and 69%, respectively . Distant metastasis was detected in 11.57% of cases. The data were based on a study of 3026 cases in America between 1973 and 2003. In addition, Gomez DR et al., in 2008, reported the 5-year and 10-year survival was 87% and 65%, respectively . Distant metastasis was detected in 34% of cases. The study was based on 59 cases. The differences between their data and the present study were analyzed in terms of the following: (1) the outcome for patients with ACC in the lacrimal gland and sinonasal subsite was poorer than those with ACC in the salivary gland. Although our study did not reveal that survival was associated with the subsite, it was reported that 5-year survival for patients with sinonasal ACC was from 50% to 62.9% [7, 8]. Lacrimal gland ACC and paranasal sinus ACC accounted for 60.0% in our data, 42.4% in Gomez DR’s and 5.12% in Ellington CL’s. More patients with lacrimal gland and sinonasal ACC decreased our survival. (2) There were more patients (60%) in advanced stage in our cohort, compared with Ellington’s (47.95%) and Gomez’s (47.5%). (3) Females had better survival outcomes, as concluded by Ellington CL and Lloyd . The male-to-female ratio was 1:1.1 in our data, 1:1.9 in Gomez DR’s and 1:1.4 in Ellington CL’s. Unfortunately, the relationship between sex and survival was not confirmed in our study. (4) None of our patients received chemotherapy, whereas some patients of the other studies did, including cisplatin, 5-fluorouracil and anthracyclines. Although chemotherapy showed inconsistent results, some patients did benefit from it. (5) Higher grade related to poorer outcome. 17.6% of cases in our study were grade 3 or higher. The other two studies did not list the histological grade; therefore, the patients might be in different grades which would eventually cause differences in outcomes. (6) All patients in our study were Chinese. Asian and Pacific Islanders accounted for only 7.77% in Ellington CL’s study and none in Gomez DR’s. Race might play a role. (7) The social and economic position should not be ignored in medical behavior. Despite explanations for the differences, further studies are required to confirm that a “high risk” carcinoma can still have an excellent patient outcome.
CD117 (KIT) is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. KIT is activated by binding of its ligand, which leads to a phosphorylation cascade ultimately activating various transcription factors in different cell types. CD117 has been detected in many normal cells and tumor cells . Previous studies have shown that 78% to 100% of ACC expressed CD117 [10–15]. But only Mino M et al. briefly discussed the relationship between the pattern of immunostaining and the different histological subtypes. Mino’s data were based on a cohort of 66 cases. The data revealed that the solid subtype of ACC showed a mostly diffuse pattern and the tubular and cribriform subtypes demonstrated CD117 expression primarily within the luminal epithelial cell layer, which was p63 negative. The authors, however, did not discuss CD117 expression in p63-positive cells.
Our study focused on the immunostaining patterns, not only in p63-negative cells but also in p63-positive cells, and compared the patterns with histology grades and prognosis. Our study revealed that the P63-/CD117+ pattern was not associated with histological grade or prognosis in either stage. Interestingly, the P63+/CD117+ pattern was not related to grade or prognosis in the early stage. It was, however, significantly related to grade and prognosis in the advanced stage. Increased numbers of P63+/CD117+ cells meant a higher histological grade and a poorer prognosis. The current theory was that the organ stem cell with pluripotent differentiation capability would unidirectionally differentiate toward myoepithelia (p63-positive cells) or glandular epithelia (p63-negative cells) in ACC. Since myoepithelia has cytoplastic smooth muscle fibril, and smooth muscle cells are constantly negative for CD117, it is inferred that the p63-positive/CD117-positive cells are tumor cells with less differentiation toward myoepithelia. Once the differentiation is extensively insignificant (meaning p63-positive cells remarkably decrease or are absent), high grade transformation will be present, which was once called dedifferentiation.
Our study also revealed the different significance of p63+/CD117+ cells in early stage and advanced stage, respectively. In addition to the non-relationship between stage and prognosis, it was thought that ACC in different stages were heterogenous.