Page 45 - ARNM-3-3

Advances in Radiotherapy
& Nuclear Medicine PI3K and Akt in androgen-independent PCa

A B C

D E F

Figure 1. Histopathological features of prostate cancer. (A-C) AIPC: (A) Crowded glands, (B) few well-formed glands, and (C) tumor cells arranged in
clusters. (D-F) ADPC: (D) Well-formed glands, (E) fused glands, and (F) minimal number of glands. Scale bar: 100 μm; magnification: 20×.
Abbreviations: ADPC: Androgen-dependent prostate cancer; AIPC: Androgen-independent prostate cancer.

glandular structure, with only a few well-formed glands morphology was characterized by a lack of glandular
present (Figure 1B). structures with necrosis, or patchy or trabecular
arrangements (Figure 1F). The carcinomatous
A total of 11 cases (28.9%) were categorized into the GS
9 – 10 category (grade group 5). The cancer cells appeared in glands were well-preserved without atrophy or
distortion. Cell boundaries were distinct, the nuclear
clumps or trabecular arrangements (Figure 1C). Cancerous membrane appeared smooth, the nuclear chromatin
glands were atrophied and distorted, with enlarged cell volume
and indistinct boundaries. The cytoplasm was flocculent or was granular, and nucleoli were prominent. The
foamy, often with vacuolar changes. Nuclear staining was stroma may have exhibited fibroblast proliferation,
but hyalinization or fibrosis was not observed
intensified, with thickened and irregular nuclear membranes. (Figure 1).
Condensed chromatin was frequently observed adjacent to
the nuclear membrane, and several shrunken nucleoli were 3.3. Immunohistochemical staining results
visible either centrally or peripherally, often with indistinct
boundaries. In addition, there was a proliferation of interstitial Positive expression of AR, PI3K, and phosphorylated
fibroblasts, along with focal hyalinization or fibrosis. Akt indicated the localization of the protein in the
nucleus (brownish-yellow), cytoplasm (light yellow or
In the ADPC group, all 38 patients were classified into brownish-yellow), and both the cytoplasm and nucleus
five grade groups based on their GSs: (brownish-yellow), respectively (Figure 2).
(i) Five patients (5/38, 18.4%) were in the GS 6 category
(grade group 1). Microscopically, intact and 3.4. Expression of AR in the two patient groups
individually separated glands were observed. There was no significant difference in AR expression
(ii) A total of 11 patients (11/38, 28.9%) were in the GS between the AIPC and ADPC groups (p > 0.05). This
7 (3 + 4) category (grade group 2). The pathological finding suggests that, although AIPC patients underwent
structure was mainly composed of well-formed hormone blockade therapy, disease progression may be
glands, with few fused or cribriform structures. associated with abnormal AR activation, activation of the
(iii) Seven patients (7/38, 18.4%) were in the GS 7 (4 + 3) PI3K/Akt pathway, or the interaction between AR and
category (grade group 3). The histological structure the PI3K/Akt pathway. AR may also be activated through
consisted mainly of poorly developed, fused, or alternative signaling pathways in the absence of androgen
cribriform glands, with a few intact glands (Figure 1D). or under hypoandrogenic conditions (Table 2).
(iv) Seven patients (7/38, 18.4%) were in the GS 8 category
(grade group 4). Some areas contained fused or 3.5. Expression of PI3K in the two patient groups
cribriform glands, while others were predominantly The expression of PI3K (+++) in the AIPC was significantly
composed of poorly differentiated components with a higher than that in the ADPC control group, with a
few well-formed glands (Figure 1E). statistically significant difference observed (p < 0.01). These
(v) Eight patients (8/38, 20.1%) were in the GS findings suggest that PI3K pathway activation may be
9 – 10 category (grade group 5). The histological closely associated with the progression of AIPC (Table 3).

Volume 3 Issue 3 (2025) 37 doi: 10.36922/ARNM025160018